Calcium dodecylbenzenesulphonate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

It is concluded that the substance Calcium dodecylbenzenesulfonate does not meet the criteria to be classified for human health hazards for Reproductive toxicity

Link to relevant study records

Reference

Reference 1

Endpoint:

fertility, other

Remarks:

based on test type

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

Dodecylbenzene sulfonic acids (CAS# 27176-87-0 , EC Number; 248-289-4) ) is a very close analogue of Calcium dodecylbenzenesulfonate (CAS No 26264-06-2, EC Number;247-557-8) ) and the dissociated acid it readily dissociates in water and release the dodecylbenzene sulfonic anion in solution.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

1) Test animals- Supplier: Orient Bio Co. Ltd. 143-1, Sangdaewon-dong, Jungwon-ku, Sungnam, Gyunggi-do, 462-120 Korea- Age at study initiation: 7-week-old animals for male and female
- No. of animals at receipt: 57 for male and female
- Body weights at study initiation: 212.5–243.8 g for males and 147.6 -168.6 g for females
- Age at the first day of treatment: 8 weeks for male and female
- Body weight range at the first day of treatment: 274.2∼311.1 g for males and 175.7∼213.4 g for females
- All animals were visually examined on acquisition. Only the animals remained in good physical condition during the 6-day acclimatization in the animal room were selected for the test.
2) Environmental condition
- Temperature 23 +/- 3 deg C, relative humidity of 50 +/- 10%; ventilation of 10 to 20 times/hours; light/dark cycle 12 h/12 h
- All animals used in this study were cared for in accordance with the principles outlined in the "Guide for the Care and Use of Laboratory Animals", a NIH publication.
3) Monitoring- Room temperature was generally in the range 20-26 deg C, relative humidity was generally in the range 40-60%. No significant deviations, which can affect the experiment, were observed.
4) Housing and identification of animals- Equal or less than five for the quarantine and acclimatization
- Equal or less than two for the pre-mating, treatment and recovery period5) Diet, water and bedding material
- Pelleted maintenance diet and tap water ad libitum; no contaminants (analysed)

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on mating procedure:

- Premating exposure period for males and females: 2 weeks

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The test article of the highest dose group was mixed with water for injection, and the low dose group's test article was prepared by dilution of that of the highest dose group. The test article solutions were prepared once a day before completion of the analytical method validation, and after completion the test article was formulated over once a week.

Duration of treatment / exposure:

From 2 weeks before mating to the end of -the mating period for male (at least 28 days)From 2 weeks before mating to day 4 of lactation including the mating and gestation periods for female- Post exposure period: 15 days in both sexes

Frequency of treatment:

Once daily

Remarks:

Doses / Concentrations:
nominal conc. 0, 100, 200, and 400 mg/kg bw/day (Dosing volume 10mL/kg/day)
Basis:
nominal conc.

No. of animals per sex per dose:

10 males and females for 100 and 200 mg/kg bw/day and 16 males and females for 400 mg/kg bw/day (10 was for test group and 6 was for recovery group), 16 males and females for vehicle control (10 was for test group and 6 was for recovery group)

Control animals:

yes

Details on study design:

Treatment- Dose levels determined in a pilot toxicity study of dodecylbenzenesulfonic acid in rats- Constant dosage volume of 10 mL/kg bw/day: calculated with Path/Tox system according to the basis of recently measured body weight.- Dosing of both sexes was begun at 2 weeks prior to mating. Dosing was continued in both sexes during the mating period. Males were dosed after the mating period at least until the minimum total dosing period of 28 days had been completed. Daily dosing of the parental females was continued throughout pregnancy and at least up to day 4 post-partum.

Parental animals: Observations and examinations:

- Mating: The day verified by sperm in a vaginal rinse was designated as day 0 of pregnancy. Based on the results, following indices were calculated. Mating index = (No. of animals with successful copulation / No. of mated animals) × 100 Fertility index = (No. of impregnating animals / No. of animals with successful copulation) × 100 Pregnancy index = (No. of pregnant animals / No. of animals with successful copulation) × 100
- Observation on gestation and parturition: Abortion, premature delivery and dystocia or prolonged parturition were observed.
- Observation on parturition date: Gestation length, delivery index, litter size, sex ratio, external anomalies of live pups were observed.
- Observation during the lactation period: Nursing behaviours of dams and viability of pups were observed. Following data were obtained from these observations. Pregnancy periodDelivery index: No. of dams with live newborns/ No. of pregnant damsx100Newborn survival index:Newborn mortality index:Viability index: No of live pups on day 4 of lactation/ No of neonates at birthx100Body weight in all survival animals on 0 and 4 days afterbirth.

Postmortem examinations (parental animals):

- Gross findings: At scheduled termination, all live animals were anaesthetized by isoflurane inhalation, blood samples taken and then terminated by exsanguinating the abdominal aorta. Complete gross post mortem examinations were performed on all animals.
- Organ weights: Absolute organ weights were measured and their relative organ weights (organ-to-body weight ratios) were calculated from the terminal body weight for the following organs of selected six animals when they were sacrificed. (Brain, pituitary gland, adrenal gland,spleen, kidneys, heart, thymus, lungs and thyroid (with parathyroid)). However, the following organs were weighed in all animals except the non-pregnant.(liver, salivary gland, testis, epididymis, seminal vesicle, prostate, ovary, uterus).
- Histopathological examination: Histopathological examination was performed on the following tissues from animals in the vehicle control and 64 mg/kg bw/day groups. abnormal lesion, skin (included mammary gland in females), urinary bladder, pancreas, mesenteric lymph node, stomach, duodenum, jejunum, ileum, cecum, colon, rectum, kidneys, adrenal glands,mandibular lymph node, thyroid (included parathyroid), aorta, thymus, heart, lungs, tongue, trachea, esophagus, sciatic nerve, skeletal muscle, sternum, femur, eye with optic nerve, haderian gland, brain, pituitary gland, spinal cord (thoracic) and nasal cavity. Additional examination was conducted in spleen, femur and sternum of the 4 and 16 mg/kg bw/day groups, since treatment-related findings were observed in these organs. Neutral buffered 10% formalin was used for fixation and preservation, except testis, epididymides and eyeballs. Bouin’s fixative was used for testis and epididymides and Davidson’s solution for eye ball. Lungs and urinary bladder were inflated with fixative prior to immersion in fixative. And then organs were embedded in paraffin, sectioned, stained with hematoxylin and eosin (H&E), and examined microscopically.

Statistics:

- Body weights, food consumption, organ weights, and clinical pathology : means the standard deviation of each mean. - Bartlett's test : analyzing for homogeneity of variance- Dunnett's t test : analyzing for the significance of inter-group differences- Analysis of Variance : analyzing for homogeneous data- Kruskal-Wallis test : analyzing for Heterogeneous data- Dunn's Rank Sum test : analyzing for the significance of inter-group differences between the control and treated groups- F test : analyzing the data of recovery groups for homogeneity of variance- Dunnett's t test : analyzing for homogeneous data- Dunn's Rank Sum test : analyzing for the significance of inter-group differences- t test : analyzing for Heterogeneous data- Kruskal-Wallis test : analyzing for the significance of inter-group differences between the control and treated group-Statistical analyses were performed by comparing the different dose groups with the vehicle control group using Path/Tox System.- p<0.05 or p<0.01

Histopathological findings: non-neoplastic:

no effects observed

Reproductive performance:

no effects observed

There were no treatment-related changes in precoital time, mating index, fertility index and pregnancy index.Results for F0- Precoital time, fertility and mating data: There were no statistically significant differences compared with the controls.- Gross findings: There were no chemical- related findings in all treatment groups.- Histopathological findings: There were no chemical- related findings in all treatment groups.

Dose descriptor:

NOAEL

Effect level:

400 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No statistically significant differences were seen in the following parameters examined: gestation length, the number of corpora lutea and implantation, delivery index, precoital time, fertility, mating data and in the histopathological examination.

Clinical signs:

not examined

Remarks on result:

not measured/tested

Reproductive effects observed:

not specified

Conclusions:

There were no treatment-related changes were observed in copulation, fertility and pregnancy indices, gestation length, the number of corpora lutea and implantation, delivery index. Based on these effects, the NOAEL (no-observed-adverse-effect levels) for fertility was 400 mg/kg bw/day.

Executive summary:

Effects on Fertility

In reproductive toxicity study performed according to the reproduction/developmental toxicity screening test [OECD TG 422] conditions and dose were same as repeated dose toxicity. A distilled water for injection was used as vehicle.

No statistically significant differences were seen in the following parameters examined: gestation length, the number of corpora lutea and implantation, delivery index, precoital time, fertility, mating data and in the histopathological examination. The NOAEL was 400 mg/kg bw/day in both sexes.

Reference 2

Endpoint:

three-generation reproductive toxicity

Remarks:

based on test type

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Benzenesulfonic acid, C10-14-alkyl derivs., sodium salts is a very close analogue of Calcium dodecylbenzenesulfonate (CAS No 26264-06-2, EC Number; 247-557-8) ) and read-across is valid.

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: Na-LAS (chain length distribution C10-14) was fed for 84 days to 4 groups of weanling rats (3 dose levels, plus control), each dose consisting of 50 animals each of both sexes (PO-generation). When the P0 generation was 107-112 days old, 20 females from each dose group were mated with 20 males from the same group and maintained together for 17 days. The first litters of each generation (Fla- and F2a-generation) were sacrificed at 21 days of age. Ten days after the final litter was sacrificed, all females were remated with different males from the same group to obtain the F1b generation. From the Flb-generation, 20 males and females of each group were selected at weaning to continue their respective diets and to be used for further reproduction studies. Reproduction studies on the F1b and F2b generations were started when the rats were 80 to 85 days old, and were continued until the F3b generation was weaned.

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

other: Charles River

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation: (P) weanling; (F1) 21 days
- Weight at study initiation: (P) Males: average 59.4-59.9 g; Females: average 57.0-57.3 g; (F1) Males: group weight 183.5-214.2 g; Females: group weight 157.8-193.2 g
- Housing: individual wire bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 76 +/- 3
- Humidity (%): 50 +/- 5
- Photoperiod (hrs dark / hrs light): 12/12 hrs

Route of administration:

oral: feed

Vehicle:

other: LAS was administered in feed (Purina Laboratory Meal) - no documentation of dilution prior to addition to meal

Details on mating procedure:

premating exposure period 84 days

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

2 years ( 3 generations)

Frequency of treatment:

continuous in feed

Details on study schedule:

- F1 parental animals not mated until 80-85 days old
- Selection of parents from F1 generation when pups were 21 days of age.
- Age at mating of the mated animals in the study: 107-112 days old

Remarks:

Doses / Concentrations:
0.02, 0.1, 0.5% (14, 70, 350 mg/kg bw d)
Basis:
actual ingested

No. of animals per sex per dose:

50 males and 50 females per group.

Control animals:

yes, concurrent no treatment

Litter observations:

Deformities and number of pups, average body weights, feed consumption, feed efficiency.

Postmortem examinations (parental animals):

Necropsy, body weight, organ to body weight ratios, routine hematology and histology.

Postmortem examinations (offspring):

Necropsy, body weight, organ to body weight ratios, routine hematology and histology.

Reproductive indices:

fertility, gestation, parturition, neonatal viability, lactation, and post-weaning growth

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Description (incidence and severity):

no effects to body weight were noted in the initial twelve weeks

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

no effects to body weight were noted in the initial twelve weeks

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

no effects observed

Description (incidence and severity):

Test substance intake: no effects to average food consumption were noted in the initial twelve weeks

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

No mortality or clinical signs were observed in parental animals. A statistically significant decrease in liver weights was noted in male rats at the low and mid dose levels at the 8 month sacrifice. As the decreased liver weight was within normal range, was not seen at the highest dose level, nor was seen at the 15 and 24 month sacrifices, it was not considered biologically significant. Body weight gains and organ to body weight ratios were normal. Gross examination revealed no abnormalities attributable to the test substance. General reproduction including fertility, gestation, parturition, neonatal viability, lactation, and post-weaning growth were normal for all test groups and did not vary from controls.

Dose descriptor:

NOAEL

Effect level:

350 mg/kg bw/day

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: 0.5%

Clinical signs:

not specified

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

Rats sacrificed at weaning were normal with respect to growth, organ to body weight ratios, gross pathology, and histology, and did not vary from controls. There were a number of statistically significant hematologic values, though these differences were small and did not indicate a trend or pattern.

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

350 mg/kg bw/day

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: 0.5%

Dose descriptor:

NOAEL

Generation:

F2

Effect level:

350 mg/kg bw/day

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: 0.5%

Reproductive effects observed:

not specified

Conclusions:

NOAEL Parental: 350 mg/kg bw/day, NOAEL F1 Offspring: 350 mg/kg bw/day, NOAEL F2 Offspring: 350 mg/kg bw/day
No significant effects on reproduction were observed at the highest concentration tested.
Na-LAS was fed for 84 days to 4 groups of weanling rats for two years (three generations). No significant effects were observed at the highest dose tested and the resulting NOAEL for the parental and both offspring generations was 350 mg/kg bw (0.5%).

Executive summary:

A three-generation reproduction study was conducted on male/female rats. LAS was administered in the diet at doses of 0.02, 0.1, 0.5% (14, 70, 350 mg/kg bw/day). A control group was used. Animals were fed for 84 days to the 4 groups of weaning rats, each consisting of 50 animals of both sexes (FO-generation). Twenty females from each dose group were mated with 20 males from the same group. The first litters of each generation (F1a-generation) were sacrificed at 21 days of age. Ten days after the first litter was sacrificed, all females were re-mated with different males from the same group. The F2a-generation was sacrificed at the F1a-generation. From the resulting F1b-generation, 20 males and females of each group were selected at weaning to continue their respective diets for 80 to 85 days until they were mated to produce the F2b-generation. This generation was treated with LAS for a further 8 weeks and mated again. The first litter (F3a) was sacrificed; the F3b-generation was treated until the animals were weaned. General reproduction including fertility gestation, parturition, neonatal viability, lactation, and post-weaning growth was normal for all test groups and did not deviate from the controls in each generation. No gross abnormalities were noted. No definitive adverse effects due to the test material were noted in the haematology and pathology.

NOAEL Parental: 350 mg/kg bw/day

NOAEL F1 Offspring: 350 mg/kg bw/day

NOAEL F2 Offspring: 350 mg/kg bw/day

The NOAEL is the highest tested dose.

 

Reference 3

Endpoint:

three-generation reproductive toxicity

Remarks:

based on test type

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Benzenesulfonic acid, C10-14-alkyl derivs., sodium salts ) is a very close analogue of Calcium dodecylbenzenesulfonate (CAS No 26264-06-2, EC Number; 247-557-8) ) and read-across is valid.

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: CLD was administered in the diet of the rats and new batches of diet were prepared each week. Males and females of each generation (Fo, F1b, and F2b) were kept on their respective diets for 60 days. The mating period for the first litter lasted 19 days. After the weaning of the first litters, approximately 10 days, the animals were re-mated and a second litter was produced. From the second litters of the initial (Fo) and second (F1b) generations, 10 males and 20 females were selected from each group at weaning in order to form the second and third (F2b) generations, respectively.
In the parent animals, observations of signs of reaction, mortalities, food consumption, bodyweight change, pregnancy rate, mating performance, and gestation period were made throughout the study. As soon as possible (< 12 hours) after birth, all young were counted, identified by toe amputation and examined for external abnormalities. Up to day 21 post partum, animals were examined daily for dead and abnormal young. Young of the first litters and surplus young of the second litters were sacrificed and examined for abnormalities internally and externally.
Rats of the F3b generation were killed at 3 weeks old and were also examined internally and externally for abnormalities. For the F3b generation, tissue from the brain, liver, heart, pituitary, spleen, thyroid, kidneys, thymus, adrenals, lungs, gonads, pancreas, bladder, bone, bone marrow, sections of the stomach, and sections of the small and large intestines were removed and examined.

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: Charles River CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: (P) males 5 wks, females 7 weeks; (F1) x wks
- Weight at study initiation: (P) Males: 154-197 g; Females: 139-184 g; (F1) Males: x-x g; Females: x-x g
- Housing: Suspended wire cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle

Route of administration:

other: oral in diet

Vehicle:

unchanged (no vehicle)

Details on exposure:

CLD was administered in the diet of the rats and new batches of diet were prepared each week.
Males and females of each generation (Fo, F1b, and F2b) were kept on their respective diets for 60 days.
The mating period for the first litter lasted 19 days. After the weaning of the first litters, approximately 10 days, the animals were re-mated and a second litter was produced.
From the second litters of the initial (Fo) and second (F1b) generations, 10 males and 20 females were selected from each group at weaning in order to form the second and third (F2b) generations, respectively.
In the parent animals, observations of signs of reaction, mortalities, food consumption, bodyweight change, pregnancy rate, mating performance, and gestation period were made throughout the study. As soon as possible (< 12 hours) after birth, all young were counted, identified by toe amputation and examined for external abnormalities. Up to day 21 post partum, animals were examined daily for dead and abnormal young. Young of the first litters and surplus young of the second litters were sacrificed and examined for abnormalities internally and externally.
Rats of the F3b generation were killed at 3 weeks old and were also examined internally and externally for abnormalities. For the F3b generation, tissue from the brain, liver, heart, pituitary, spleen, thyroid, kidneys, thymus, adrenals, lungs, gonads, pancreas, bladder, bone, bone marrow, sections of the stomach, and sections of the small and large intestines were removed and examined.

Details on mating procedure:

The mating period for the first litter lasted 19 days. After the weaning of the first litters, approximately 10 days, the animals were re-mated and a second litter was produced. From the second litters of the initial (Fo) and second (F1b) generations, 10 males and 20 females were selected from each group at weaning in order to form the second and third (F2b) generations, respectively.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

up to > 1 year

Frequency of treatment:

continuous in diet

Details on study schedule:

Males and females of each generation (Fo, F1b, and F2b) were kept on their respective diets for 60 days.
The mating period for the first litter lasted 19 days. After the weaning of the first litters, approximately 10 days, the animals were re-mated and a second litter was produced.
From the second litters of the initial (Fo) and second (F1b) generations, 10 males and 20 females were selected from each group at weaning in order to form the second and third (F2b) generations, respectively.
In the parent animals, observations of signs of reaction, mortalities, food consumption, bodyweight change, pregnancy rate, mating performance, and gestation period were made throughout the study. As soon as possible (< 12 hours) after birth, all young were counted, identified by toe amputation and examined for external abnormalities. Up to day 21 post partum, animals were examined daily for dead and abnormal young. Young of the first litters and surplus young of the second litters were sacrificed and examined for abnormalities internally and externally.
Rats of the F3b generation were killed at 3 weeks old and were also examined internally and externally for abnormalities. For the F3b generation, tissue from the brain, liver, heart, pituitary, spleen, thyroid, kidneys, thymus, adrenals, lungs, gonads, pancreas, bladder, bone, bone marrow, sections of the stomach, and sections of the small and large intestines were removed and examined.

Remarks:

Doses / Concentrations:
0.08, 0.4, and 2.0% continuously administered throughout the three generations (40, 200 and 1000 mg/kg bw d CLD [6.8, 3.4 and 170 mg/kg bw d LAS
Basis:
nominal conc.

No. of animals per sex per dose:

10 males and 20 females per group.

Control animals:

yes, concurrent no treatment

Parental animals: Observations and examinations:

In the parent animals, observations of signs of reaction, mortalities, food consumption, bodyweight change, pregnancy rate, mating performance, and gestation period were made throughout the study

Litter observations:

Examining litter parameters, statistically significant differences were occasionally observed but they showed no consistent dosagerelated trends ove the three generations and were considered to be unrelated to treatment. The incidence of malformations was unaffected by treatment.
Additional organ weight analysis, histopathology and skeletal staining of representative young from the F3b generation revealed no changes that could be conclusively related to treatment.

Postmortem examinations (parental animals):

Necropsy, body weight, organ to body weight ratios, routine hematology and histology.

Postmortem examinations (offspring):

Necropsy, body weight, organ to body weight ratios, routine hematology and histology.

Reproductive indices:

fertility, gestation, parturition, neonatal viability, lactation, and post-weaning growth

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Description (incidence and severity):

no effects to body weight were noted

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

no effects to body weight were noted

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

no effects observed

Description (incidence and severity):

Test substance intake: no effects to average food consumption were noted

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

General parental toxicity: There were no signs of malreaction to treatment among parents and the incidence of sporadic deaths and total litter losses were unrelated to dosage. Pregnancy rate and the duration of gestation were unaffected. Food consumption and bodyweight changes showed no consistent relationship to dosage over the three generations.

Dose descriptor:

NOAEL

Effect level:

170 mg/kg bw/day

Based on:

act. ingr.

Remarks:

LAS

Sex:

male/female

Basis for effect level:

other: NOAEL Parental: 170 mg/kg bw d LAS (1000 mg/kg bw d CLD)

Clinical signs:

not specified

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

Toxicity to offspring: Examining litter parameters, statistically significant differences were occasionally observed but they showed no consistent dosage related trends over the three generations and were considered to be unrelated to treatment. The incidence of malformations was unaffected by treatment. Additional organ weight analysis, histopathology and skeletal staining of representative young from the F3b generation revealed no changes that could be conclusively related to treatment.

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

170 mg/kg bw/day

Based on:

act. ingr.

Remarks:

LAS

Sex:

male/female

Basis for effect level:

other: NOAEL F1 Offspring: 170 mg/kg bw d LAS (1000 mg/kg bw d CLD)

Dose descriptor:

NOAEL

Generation:

F2

Effect level:

170 mg/kg bw/day

Based on:

act. ingr.

Remarks:

LAS

Sex:

male/female

Basis for effect level:

other: NOAEL F2 Offspring: 170 mg/kg bw d LAS (1000 mg/kg bw d CLD)

Reproductive effects observed:

not specified

Conclusions:

NOAEL Parental: 170 mg/kg bw/day, NOAEL F1 Offspring: 170 mg/kg bw/day, NOAEL F2 Offspring: 170 mg/kg bw/day
No significant effects on reproduction were observed at the highest concentration tested.
The NOAEL for LAS is 170 mg/kg bw/day, corresponding to the highest tested dose

Executive summary:

General parental toxicity: There were no signs of malreaction to treatment among parents and the incidence of sporadic deaths and total litter losses were unrelated to dosage. Pregnancy rate and the duration of gestation were unaffected. Food consumption and bodyweight changes showed no consistent relationship to dosage over the three generations.

Toxicity to offspring: Examining litter parameters, statistically significant differences were occasionally observed but they showed no consistent dosage related trends over the three generations and were considered to be unrelated to treatment. The incidence of malformations was unaffected by treatment. Additional organ weight analysis, histopathology and skeletal staining of representative young from the F3b generation revealed no changes that could

be conclusively related to treatment

NOAEL Parental: 170 mg/kg bw d LAS (1000 mg/kg bw d CLD)

NOAEL F1 Offspring: 170 mg/kg bw d LAS (1000 mg/kg bw d CLD)

NOAEL F2 Offspring: 170 mg/kg bw d LAS (1000 mg/kg bw d CLD)

 

Reference 4

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

other: QSAR Estrogen Receptor Binding method

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

QSAR prediction: Accepted Estrogen Receptor Binding QSAR method for chemicals properties assessment.. This method is relevant for reproductive toxicity endpoints in fish and mammals.

Qualifier:

according to guideline

Guideline:

other: QSAR Toolbox Version 3.3.5.17

Principles of method if other than guideline:

This grouping method contains simple categories for estrogen receptor (ER) binding. This method is relevant for reproductive toxicity endpoints in fish and mammals.
Estrogen receptor (ER) binding is a molecular initiating event much like protein binding. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER binding and possible subsequent endocrine disruption.

The incorporated Toolbox ER binding profiling scheme is based on structural and parametric rules extracted from literature sources and supported by experimental data . The ER-binding profiler clasifies chemicals as non binders or binders depending on molecular weight (MW) and structural characteristics of the chemicals:
1. Very strong binders: Chemicals with MW between 200 and 500 Da and two rings with a hydroxyl group connected to each of them.
2.Strong binders: Chemicals with at least one 5-or 6-members carbon ring with an unhindered hydroxyl or amino group and MW between 200 and 500 Da;
3.Moderate binders: Chemicals with at least one 5-or 6-members carbon ring with an unhindered hydroxyl or amino group and MW between 170 and 200 Da;
4. Weak binders: Chemicals with at least one 5-or 6-members carbon ring with an unhindered hydroxyl or amino group and MW less than 170 Da;

If the target chemical does not meet some of the structural and parametric requirements listed above it is classified as Non binder:
Non binder with impaired hydroxyl or amino group;
Non binder, MW more than 500 Da;
Non binders without hydroxyl or amino group;
Non-binder, non-cyclic.

GLP compliance:

no

Remarks:

not applicable. QSAR model,Estrogen Receptor Binding method, relevant for reproductive toxicity endpoints in fish and mammals.

Limit test:

no

Species:

other: fish (trout) and mammals.

Strain:

other: QSAR model

Sex:

not specified

Route of administration:

other: QSAR model

Vehicle:

other: QSAR model

Details on exposure:

Estrogen receptor (ER) binding is a molecular initiating event much like protein binding that leads to a series of adverse outcomes, which are typically considered reproductive and development hazards. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER-binding and possible endocrine disruption .

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Estrogen receptor (ER) binding is a molecular initiating event much like protein binding that leads to a series of adverse outcomes, which are typically considered reproductive and development hazards. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER-binding and possible endocrine disruption .

Remarks:

Doses / Concentrations:

Basis:
other: QSAR model

Control animals:

not specified

Parental animals: Observations and examinations:

Estrogen receptor (ER) binding is a molecular initiating event much like protein binding that leads to a series of adverse outcomes, which are typically considered reproductive and development hazards. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER-binding and possible endocrine disruption .

Clinical signs:

no effects observed

Description (incidence and severity):

QSAR model

Body weight and weight changes:

no effects observed

Description (incidence and severity):

QSAR model

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

QSAR model

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

QSAR model

Other effects:

no effects observed

Description (incidence and severity):

Test substance intake: QSAR model

Reproductive function: oestrous cycle:

no effects observed

Description (incidence and severity):

QSAR model

Reproductive function: sperm measures:

no effects observed

Description (incidence and severity):

QSAR model

Reproductive performance:

no effects observed

Description (incidence and severity):

QSAR model

Non-ER binder due to non-cyclic molecular structure.Calcium dodecylbenzenesulphonate have a molecular weight greater than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Calcium dodecylbenzenesulphonate does not cause reproductive toxicity.

1.1. CAS number: 80206-82-2
1.2. Chemical name(s):
Alcohols, C12-14
1.3. Structure codes:
a. SMILES: CCCCCCCCCCCCO
1.4. Profiling results:
-DNA binding by OECD -No alert found
-Estrogen Receptor Binding-Non binder, non cyclic structure
-OECD HPV Chemical Categories-Long chain alcohols
-Protein binding by OECD-No alert found
-US-EPA New Chemical Categories-Neutral Organics
-Toxic hazard classification by Cramer (original)-Low (Class I)

Key result

Dose descriptor:

other: Relative ERBA (Estrogen Receptor Binding Affinity)

Effect level:

< -3 other: Log RBA(Relative Binding Affinities )

Based on:

other: Estrogen receptor (ER) binding

Sex:

not specified

Basis for effect level:

reproductive performance

Remarks on result:

other:

Remarks:

Non-ER binder due to non-cyclic molecular structure.Calcium dodecylbenzenesulphonate have a molecular weight greater than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Calcium dodecylbenzenesulphonate does not cause reproductive toxicity.

Clinical signs:

no effects observed

Description (incidence and severity):

QSAR model

Mortality / viability:

no mortality observed

Description (incidence and severity):

QSAR model

Body weight and weight changes:

no effects observed

Description (incidence and severity):

QSAR model

Sexual maturation:

no effects observed

Description (incidence and severity):

QSAR model

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

QSAR model

Gross pathological findings:

no effects observed

Description (incidence and severity):

QSAR model

Histopathological findings:

no effects observed

Description (incidence and severity):

QSAR model

Non-ER binder due to non-cyclic molecular structure.Calcium dodecylbenzenesulphonate have a molecular weight greater than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Calcium dodecylbenzenesulphonate does not cause reproductive toxicity.

1.1. CAS number: 26264-06-2
1.2. Chemical name(s):
benzenesulfonic acid, dodecyl-, calcium salt
calcium dodecylbenzenesulphonate
dodecylbenzenesulfonic acid, calcium salt
1.3. Structure codes:
a. SMILES: CCCCCCCCCC(CC)c1ccc(S(=O)(=O)O{-}.[Ca]{2+}.O{-}S(=O)(=O)c2ccc(C(CC)CCCCCCCCC)cc2)cc1
1.4. Profiling results:
-DNA binding by OECD -No alert found
-Estrogen Receptor Binding-Non binder, MW>500
-OECD HPV Chemical Categories-Not categorized
-Protein binding by OECD-No alert found
-US-EPA New Chemical Categories-Not categorized

Key result

Dose descriptor:

other: Relative ERBA (Estrogen Receptor Binding Affinity)

Generation:

F1

Effect level:

< -3 other: Log RBA(Relative Binding Affinities )

Based on:

other: Estrogen receptor (ER) binding

Sex:

not specified

Basis for effect level:

clinical signs

mortality

body weight and weight gain

gross pathology

histopathology: non-neoplastic

Remarks on result:

other:

Remarks:

Non-ER binder due to non-cyclic molecular structure.Calcium dodecylbenzenesulphonate have a molecular weight greater than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Calcium dodecylbenzenesulphonate does not cause reproductive toxicity.

Reproductive effects observed:

not specified

This grouping method contains simple categories for estrogen receptor (ER) binding. This method is relevant for reproductive toxicity endpoints in fish and mammals.

 

Non-binder, impaired OH or NH2 group

Non-binder without OH or NH2 group

Non-binder, non-cyclic structure

Non-binder, MW > 500

Non-binder, non-cyclic structure– chemicals without cycles and MW =<500

Non-ER binder due to non-cyclic molecular structure.

 

Estrogen receptor (ER) binding is a molecular initiating event much like protein binding that leads to a series of adverse outcomes, which are typically considered reproductive and development hazards. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER-binding and possible endocrine disruption .

Popular among these are the “four phase” assessment that includes Comparative Molecular Field Analysis (CoMFA) and the Common Reactivity Pattern Approach (COREPA)

Since the RE-binding is a receptor mediated event, particular organic functional groups, size and shape are critical to binding potency.

Calcium dodecylbenzenesulphonate have a molecular weight greater than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Calcium dodecylbenzenesulphonate does not cause reproductive toxicity.

 

 

Conclusions:

Non-ER binder due to non-cyclic molecular structure.Calcium dodecylbenzenesulphonate have a molecular weight greater than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Calcium dodecylbenzenesulphonate does not cause reproductive toxicity.

Executive summary:

Non-ER binder due to non-cyclic molecular structure.Calcium dodecylbenzenesulphonate have a molecular weight greater than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Calcium dodecylbenzenesulphonate does not cause reproductive toxicity.

1.1. CAS number: 26264-06-2

1.2. Chemical name(s):

benzenesulfonic acid, dodecyl-, calcium salt

calcium dodecylbenzenesulphonate

dodecylbenzenesulfonic acid, calcium salt

1.3. Structure codes:

a. SMILES: CCCCCCCCCC(CC)c1ccc(S(=O)(=O)O{-}.[Ca]{2+}.O{-}S(=O)(=O)c2ccc(C(CC)CCCCCCCCC)cc2)cc1

1.4. Profiling results:

-DNA binding by OECD -No alert found

-Estrogen Receptor Binding-Non binder, MW>500

-OECD HPV Chemical Categories-Not categorized

-Protein binding by OECD-No alert found

-US-EPA New Chemical Categories-Not categorized

Reference 5

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

other: QSAR model

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

QSAR prediction:Accepted Estrogen Receptor Binding QSAR method for chemicals properties assessment.. This method is relevant for reproductive toxicity endpoints in fish and mammals.

Qualifier:

according to guideline

Guideline:

other: Estrogen Receptor Binding method

Principles of method if other than guideline:

This grouping method contains simple categories for estrogen receptor (ER) binding. This method is relevant for reproductive toxicity endpoints in fish and mammals.

GLP compliance:

no

Remarks:

not applicable. QSAR model

Limit test:

no

Species:

other: fish and mammals.

Strain:

other: QSAR model

Sex:

not specified

Route of administration:

other: QSAR model

Vehicle:

other: QSAR model

Details on exposure:

Estrogen receptor (ER) binding is a molecular initiating event much like protein binding that leads to a series of adverse outcomes, which are typically considered reproductive and development hazards. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER-binding and possible endocrine disruption .

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Estrogen receptor (ER) binding is a molecular initiating event much like protein binding that leads to a series of adverse outcomes, which are typically considered reproductive and development hazards. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER-binding and possible endocrine disruption .

Remarks:

Doses / Concentrations:

Basis:
other: QSAR model

Control animals:

not specified

Parental animals: Observations and examinations:

Estrogen receptor (ER) binding is a molecular initiating event much like protein binding that leads to a series of adverse outcomes, which are typically considered reproductive and development hazards. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER-binding and possible endocrine disruption .

Clinical signs:

no effects observed

Description (incidence and severity):

QSAR model

Body weight and weight changes:

no effects observed

Description (incidence and severity):

QSAR model

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

QSAR model

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

QSAR model

Other effects:

no effects observed

Description (incidence and severity):

Test substance intake: QSAR model

Reproductive function: oestrous cycle:

no effects observed

Description (incidence and severity):

QSAR model

Reproductive function: sperm measures:

no effects observed

Description (incidence and severity):

QSAR model

Reproductive performance:

no effects observed

Description (incidence and severity):

QSAR model

No binding to Estrogen Receptor Alpha (Log RBA <-3) for the Calcium dodecylbenzenesulphonate) (CAS# 26264-06-2)

Key result

Dose descriptor:

other: QSAR model

Effect level:

< -3 other: Log RBA

Based on:

other: Estrogen receptor (ER) binding

Sex:

not specified

Basis for effect level:

clinical signs

body weight and weight gain

gross pathology

histopathology: non-neoplastic

reproductive performance

Remarks on result:

other:

Remarks:

No binding to Estrogen Receptor Alpha (Log RBA <-3) for the Calcium dodecylbenzenesulphonate) (CAS# 26264-06-2)

Clinical signs:

no effects observed

Description (incidence and severity):

QSAR model

Mortality / viability:

no mortality observed

Description (incidence and severity):

QSAR model

Body weight and weight changes:

no effects observed

Description (incidence and severity):

QSAR model

Sexual maturation:

no effects observed

Description (incidence and severity):

QSAR model

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

QSAR model

Gross pathological findings:

no effects observed

Description (incidence and severity):

QSAR model

Histopathological findings:

no effects observed

Description (incidence and severity):

QSAR model

No binding to Estrogen Receptor Alpha (Log RBA <-3) for the Calcium dodecylbenzenesulphonate (CAS# 26264-06-2) and therefore Calcium dodecylbenzenesulphonate does not cause reproductive toxicity.

Key result

Dose descriptor:

other: QSAR model

Generation:

F1

Effect level:

< -3 other: Log RBA

Based on:

other: Estrogen receptor (ER) binding

Sex:

not specified

Basis for effect level:

clinical signs

body weight and weight gain

gross pathology

histopathology: non-neoplastic

Remarks on result:

other:

Remarks:

No binding to Estrogen Receptor Alpha (Log RBA <-3) for the Calcium dodecylbenzenesulphonate) (CAS# 26264-06-2)

Reproductive effects observed:

not specified

No binding to Estrogen Receptor Alpha (Log RBA <-3) for the Calcium dodecylbenzenesulphonate (CAS# 26264-06-2) and therefore Calcium dodecylbenzenesulphonate does not cause reproductive toxicity.

Conclusions:

No binding to Estrogen Receptor Alpha (Log RBA <-3) for the Calcium dodecylbenzenesulphonate (CAS# 26264-06-2) and therefore Calcium dodecylbenzenesulphonate does not cause reproductive toxicity.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

400 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

 

Effect on fertility: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

17.4 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

Inhalation exposure:
There are no Inhalation reproduction studies available.
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.
NOAEL rat
400 mg/kg bw/day
÷1.15 m3/kgbw
÷20m3/rat
NOAECrat 17.4 mg/m3

Effect on fertility: via dermal route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

10 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

There are no dermal reproduction studies available.
For dermal exposure we taken that:
-the average weight of rats is 250g (200-300g),
-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg
corrected dermal NOAEL= oral NOAEL
400 mg/kg bw/day x 0.025 kg =
NOAELrat = 10 mg/kg bw/day

Additional information

Non-ER binder due to non-cyclic molecular structure.Calcium dodecylbenzenesulphonate have a molecular weight greater than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Calcium dodecylbenzenesulphonate does not cause reproductive toxicity.

Oral exposure

In reproductive toxicity study performed according to the reproduction/developmental toxicity screening test [OECD TG 422] under GLP, test conditions and dose were same asrepeated dose toxicity. A distilled water for injection was used as vehicle.

No statistically significant differences were seen in the following parameters examined: gestation length, the number of corpora lutea and implantation, delivery index, precoital time, fertility, mating data and in the histopathological examination.

The NOAEL was 400 mg/kg bw/day in both sexes.

            

 NOAELrat  =400 mg/kg bw/day

Dermal exposure:

There are no dermal reproduction studies available.

For dermal exposure we taken that:

-the average weight of rats is 250g (200-300g),

-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg

 corrected dermal NOAEL=   oral NOAEL

400 mg/kg bw/day x 0.025 kg =                  

 NOAELrat  = 10 mg/kg bw/day

Inhalation exposure:

The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m³), assuming 100 % absorption for both routes.

NOAEL rat             

 400mg/kg bw/day

÷1.15m3/kgbw

÷20m3/rat

NOAECrat     17.4 mg/m3 

Short description of key information:
There are conclusive but not suffcient data for the classification of substance Calcium dodecylbenzenesulfonate with regard to reproduction.
It is concluded that the substance Calcium dodecylbenzenesulfonate does not meet the criteria to be classified for human health hazards for Reproductive toxicity. Non-ER binder due to non-cyclic molecular structure.Calcium dodecylbenzenesulphonate have a molecular weight greater than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Calcium dodecylbenzenesulphonate does not cause reproductive toxicity.

Justification for selection of Effect on fertility via inhalation route:
Inhalation exposure:
There are no Inhalation reproduction studies available.
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.
NOAEL rat
400 mg/kg bw/day
÷1.15 m3/kgbw
÷20m3/rat
NOAECrat 17.4 mg/m3

Effects on developmental toxicity

Description of key information

There are conclusive but not suffcient data for the classification of substance Calcium dodecylbenzenesulfonate with regard to Developmental toxicity / teratogenicity 

Link to relevant study records

Reference

Reference 1

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Dodecylbenzene sulfonic acids (CAS# 27176-87-0 , EC Number; 248-289-4) ) is a very close analogue of Calcium dodecylbenzenesulfonate (CAS No 26264-06-2, EC Number;247-557-8) ) and the dissociated acid it readily dissociates in water and release the dodecylbenzene sulfonic anion in solution.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: OECD TG 422 “Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test in rats"

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

1) Test animals- Supplier: Orient Bio Co. Ltd. 143-1, Sangdaewon-dong, Jungwon-ku, Sungnam, Gyunggi-do, 462-120 Korea- Age at study initiation: 7-week-old animals for male and female- No. of animals at receipt: 57 for male and female- Body weights at study initiation: 212.5-243.8 g for males and 147.6 -168.6 g for females- Age at the first day of treatment: 8 weeks for male and female- Body weight range at the first day of treatment: 274.2-311.1 g for males and 175.7-213.4 g for females- All animals were visually examined on acquisition. Only the animals remained in good physical condition during the 6-day acclimatization in the animal room were selected for the test.
2) Environmental condition- Temperature 23 +/- 3 deg C, relative humidity of 50 +/- 10%; ventilation of 10 to 20 times/hours; light/dark cycle 12 h/12 h- All animals used in this study were cared for in accordance with the principles outlined in the "Guide for the Care and Use of Laboratory Animals", a NIH publication.
3) Monitoring- Room temperature was generally in the range 20-26 deg C, relative humidity was generally in the range 40-60%. No significant deviations, which can affect the experiment, were observed.
4) Housing and identification of animals- Equal or less than five for the quarantine and acclimatization- Equal or less than two for the pre-mating, treatment and recovery period5) Diet, water and bedding material- Pelleted maintenance diet and tap water ad libitum; no contaminants (analysed)

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The test article of the highest dose group was mixed with water for injection, and the low dose group's test article was prepared by dilution of that of the highest dose group. The test article solutions were prepared once a day before completion of the analytical method validation, and after completion the test article was formulated over once a week.

Details on mating procedure:

Premating exposure period for males and females: 2 weeks

Duration of treatment / exposure:

From 2 weeks before mating to the end of -the mating period for male (at least 28 days)From 2 weeks before mating to day 4 of lactation including the mating and gestation periods for female- Post exposure period: 15 days in both sexes.

Frequency of treatment:

daily

No. of animals per sex per dose:

10 males and females for 100 and 200 mg/kg bw/day and 16 males and females for 400 mg/kg bw/day (10 was for test group and 6 was for recovery group), 16 males and females for vehicle control (10 was for test group and 6 was for recovery group)

Control animals:

yes

Details on study design:

Treatment- Dose levels determined in a pilot toxicity study of dodecylbenzenesulfonic acid in rats.- Constant dosage volume of 10 mL/kg bw/day: calculated with Path/Tox system according to the basis of recently measured body weight.- Dosing of both sexes was begun at 2 weeks prior to mating. Dosing was continued in both sexes during the mating period. Males were dosed after the mating period at least until the minimum total dosing period of 28 days had been completed. Daily dosing of the parental females was continued throughout pregnancy and at least up to day 4 post-partum.

Maternal examinations:

-Observation of pregnancy and delivery-Pregnancy period-No. of implantation and corpus lutea-Delivery index=(No. of dams with live newborns/ No. of pregnant dams) x 100

Fetal examinations:

-No. of perinatal death-No. of live young on day 0 and 4 at postpartum-No. of pups with gross lesions-No. of pups with runts-Viability index at day 4 of postpartum=(No. of live pups at day 4/ No. of live pups at birth) x 100-Body weights of pups on day 0 and 4 postpartum

Statistics:

- Body weights, food consumption, organ weights, and clinical pathology : means the standard deviation of each mean. - Bartlett's test : analyzing for homogeneity of variance- Dunnett's t test : analyzing for the significance of inter-group differences- Analysis of Variance : analyzing for homogeneous data- Kruskal-Wallis test : analyzing for Heterogeneous data- Dunn's Rank Sum test : analyzing for the significance of inter-group differences between the control and treated groups- F test : analyzing the data of recovery groups for homogeneity of variance- Dunnett's t test : analyzing for homogeneous data- Dunn's Rank Sum test : analyzing for the significance of inter-group differences- t test : analyzing for Heterogeneous data- Kruskal-Wallis test : analyzing for the significance of inter-group differences between the control and treated group-Statistical analyses were performed by comparing the different dose groups with the vehicle control group using Path/Tox System. - p<0.05 or p<0.01

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Results for F0 and F1No statistically significant differences were seen in the following parameters examined: gestation length, the number of implantation, delivery index, the number of live and dead pups, live pups/implantation ratio, dead pups/implantation ratio, pre-implantation loss, post-implantation loss, sex ratio, viability index, number of neonates with external anomalies, and body weights of pups on post-natal day 0 and day 4. On the other hand, a statistically significant decrease in corpora lutea was observed in the 400 mg/kg bw/day group. But this change was in normal range and unrelated to dodecylbenzenesulfonic acid dosing.

Dose descriptor:

NOAEL

Effect level:

400 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Remarks on result:

other:

Remarks:

No statistically significant differences were seen in the following parameters examined: gestation length, the number of implantation, delivery index, the number of live and dead pups, live pups/implantation ratio, dead pups/implantation ratio, pre-implantation loss, post-implantation loss, sex ratio, viability index, number of neonates with external anomalies, and body weights of pups on post-natal day 0 and day 4.

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

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Results for F0 and F1No statistically significant differences were seen in the following parameters examined: gestation length, the number of implantation, delivery index, the number of live and dead pups, live pups/implantation ratio, dead pups/implantation ratio, pre-implantation loss, post-implantation loss, sex ratio, viability index, number of neonates with external anomalies, and body weights of pups on post-natal day 0 and day 4. On the other hand, a statistically significant decrease in corpora lutea was observed in the 400 mg/kg bw/day group. But this change was in normal range and unrelated to dodecylbenzenesulfonic acid dosing.

Dose descriptor:

NOAEL

Effect level:

400 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Embryotoxic / teratogenic effects:no effects

Remarks on result:

other:

Remarks:

Results for F0 and F1No statistically significant differences were seen in the following parameters examined: gestation length, the number of implantation, delivery index, the number of live and dead pups, live pups/implantation ratio, dead pups/implantation ratio, pre-implantation loss, post-implantation loss, sex ratio, viability index, number of neonates with external anomalies, and body weights of pups on post-natal day 0 and day 4. On the other hand, a statistically significant decrease in corpora lutea was observed in the 400 mg/kg bw/day group. But this change was in normal range and unrelated to dodecylbenzenesulfonic acid dosing.

Abnormalities:

not specified

Developmental effects observed:

not specified

Conclusions:

There were no treatment-related changes in all parameters of offsprings during the parturition and lactation periods. Based on these effects, the NOAEL (no-observed-adverse-effect levels) for developmental toxicity was 400 mg/kg bw/day of F1 pups.

Executive summary:

Developmental Toxicity

In reproductive toxicity study performed according to the reproduction/developmental toxicity screening test [OECD TG 422] conditions and dose were same as repeated dose toxicity. The offspring delivered by chemical-treated rats had been observed until day 4 of postpartum. There were no statistically significant differences were seen in the following parameters: the number of live and dead pups, live pups/implantation ratio, dead pups/implantation ratio, pre-implantation loss, post-implantation loss, sex ratio, viability index, number of neonates with external anomalies, and body weights of pups on post-natal day 0 and day 4. There were no treatment-related changes in all parameters of offsprings during the parturition and lactation periods and the NOAEL for developmental toxicity was 400mg/kg bw/day for F1 pubs.

Reference 2

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

C12 LAS; Linear Alkylbenzene Sulfonate (LAS)) is a very close analogue of Calcium dodecylbenzenesulfonate (CAS No 26264-06-2, EC Number; 247-557-8) ) and read-across is valid.

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: LAS was applied to depilated areas on the chests and backs of female rats 12- 18 weeks of age. Five to six hours prior to treatment an exposure site (roughly 24 cm2) in the dorsothoracic region of each animal from group II through IX was clipped to a length of 1 mm. The animals were reclipped every 48 hr throughout the study. Group I animals were unclipped, group II animals were clipped but not treated and group III animals were clipped and treated with tap water. The mated female rats were treated daily from day 0 through day 20 of gestation. A 0.5-ml sample of the appropriate concentration of LAS and/or tap water was applied once daily to the clipped area and spread with a gloved finger over as much of the exposure site as
possible. Each application was carried out slowly over a 3-min period. In the 1, 5 and 20% LAS groups (groups VII, VIII and IX, respectively corresponding to 20, 100 and 400 mg/kg/day) the test material was allowed to remain on the backs of the animals for 30 min. after which it was removed with warm tap water. The test material was not removed from the backs of the animals in the 0.05, 0.1 and 0.5% LAS groups (groups IV, V and VI corresponding to 1, 2 and 10 mg/kg/day). Animal body weight and food consumption were determined during the treatment period. Daily observations were also made for toxicological effects.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

- Sex: female- Age: 12-18 weeks old

Route of administration:

dermal

Details on exposure:

LAS was applied to depilated areas on the chests and backs of female rats 12- 18 weeks of age. Five to six hours prior to treatment an exposure site (roughly 24 cm2) in the dorsothoracic region of each animal from group II through IX was clipped to a length of 1 mm. The animals were reclipped every 48 hr throughout the study. Group I animals were unclipped, group II animals were clipped but not treated and group III animals were clipped and treated with tap water.

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

The mated female rats were treated daily from day 0 through day 20 of gestation. A 0.5-ml sample of the appropriate concentration of LAS and/or tap water was applied once daily to the clipped area and spread with a gloved finger over as much of the exposure site as possible. Each application was carried out slowly over a 3-min period.

Duration of treatment / exposure:

0-20 gestation meet

Frequency of treatment:

Daily

Duration of test:

sacrifice at day 21 of gestation

Control animals:

yes, concurrent no treatment

Details on study design:

Other: LAS was applied daily during the gestation period.Test group was devided into six groups by test material concentration.0.05, 0.1 and 0.5% (1, 2 and 10 mg/kg/day) (group Ⅳ Ⅴ Ⅵ) active ingredient were applied and allowed to remain on the skin. 1, 5 and 20%(20, 100 and 400 mg/kg/day) (group Ⅶ Ⅷ Ⅸ) active ingredient were applied and removed after a 30-min exposure period

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Pregnancy rates: 100% except group Ⅳ(95%) Ⅸ(95.2%).Mortality: No mortality was observed.Mean body weight: in group Ⅸ was slightly reduced from days 12-21 of the gestation period Skin change: slight skin discoloration was observed from day 3 to 6 of gestation (group Ⅶ), slight erythema and dry skin was observed from days 3 to 6 of gestation (group Ⅷ).

Dose descriptor:

NOAEL

Effect level:

20 mg/kg bw/day

Based on:

act. ingr.

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Mean number of corpora lutea, implantations, viable foetuses or resorptions : not found in any of the treatment groups. Viability and size: no relationship to LAS administration was evident.Number of thoracic and lumbar vertebrae and phalanges: no significant differences between the LAS-treated group and control group.Soft tissue: distended renal pelvis, distended ureters, ectopic testis, and distended bladder were observed but these symptoms were not considered to be related to LAS application.Skeletal and visceral abnormalities: not found in any of the treatment groups.

Dose descriptor:

NOAEL

Effect level:

400 mg/kg bw/day

Based on:

act. ingr.

Basis for effect level:

other: teratogenicity

Abnormalities:

not specified

Developmental effects observed:

not specified

Conclusions:

In maternal, there were only slight change of body weight and skin change. In foetals, no significant differences between the LAS – related group and control group were observed. Thus, LAS was not induced teratogenic or embryotoxic effects.

Executive summary:

NOAEL Maternal: 1% (20 mg/kg bw d)

NOAEL teratogenicity: 20% (400 mg/kg bw d)

Results:

Maternal toxicity:

The dams treated with 20% and 5% showed inhibition of body weight gain and local skin effects.

Teratogenicity:

There were no indications of teratogenic or embryotoxic effects at any level in either group tested.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

400 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

17.4 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

Inhalation exposure:
There are no Inhalation Developmental studies available.
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.
NOAEL rat
400 mg/kg bw/day
÷1.15 m3/kgbw
÷20m3/rat
NOAECrat 17.4 mg/m3

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

20 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

Oral exposure

In reproductive toxicity study performed according to the reproduction/developmental toxicity screening test [OECD TG 422] under GLP, test conditions and dose were same as repeated dose toxicity. The offspring delivered by chemical-treated rats had been observed until day 4 of postpartum. There were no statistically significant differences were seen in the following parameters: the number of live and dead pups, live pups/implantation ratio, dead pups/implantation ratio, pre-implantation loss, post-implantation loss, sex ratio, viability index, number of neonates with external anomalies, and body weights of pups on post-natal day 0 and day 4. There were no treatment-related changes in all parameters of offsprings during the parturition and lactation periods and the NOAEL for developmental toxicity was 400 mg/kg bw/day for F1 pubs.

NOAELrat  = 400 mg/kg bw/day

Dermal exposure:

Dermal study was conducted on female rats (days 0 through 21 of gestation), with daily exposure at 1.0%, 5.0%, and 20% of LAS (20, 100, and 400 mg/kg bw/day).

Results:

Maternal toxicity:

The dams treated with 20% and 5% showed inhibition of body weight gain and local skin effects.

Teratogenicity:

There were no indications of teratogenic or embryotoxic effects at any level in either group tested.

NOAEL Maternal: 1% (20 mg/kg bw d)

NOAEL teratogenicity: 20% (400 mg/kg bw d)

Inhalation exposure:

The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.

NOAEL rat             

 400 mg/kg bw/day

÷1.15 m3/kgbw

÷20m3/rat

NOAECrat    17.4 mg/m3

Toxicity to reproduction: other studies

Additional information

LAS  (as a read across) was injected (subcutaneous) at doses of 20 mL/kg/day from day 0 to 3 or day 8 to 11 of pregnancy.

When dams were administered the 1% solution from day 0 to 3 of pregnancy, there was an initial decrease in body weight and necrosis at the injection sites. The number of pregnancies decreased in the mice given the 1% solution compared to the controls (61.5% vs. 93.3%) There were no significant changes with respect to litter parameters, major malformations or minor abnormalities.

 

NOAEL Maternal: 0.35% (20 mg/kg bw d)

NOAEL teratogenicity : 1% (200 mg/kg bw d)

 

Justification for classification or non-classification

Based on the hazard assessment of Calcium dodecylbenzenesulfonate in section 2.1 and 2.2. in IUCLID 6., available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health” andaccording to the criteria described in Directive 67/548 and in the CLP Regulation:

Directive 67/548

Toxicity to reproduction/development Repr. Cat. 1; R61 May cause harm to the unborn child. Repr. Cat. 2; R61 May cause harm to the unborn child. Repr. Cat. 3; R63 Possible risk of harm to the unborn child. Toxicity to reproduction/fertility  Repr. Cat. 1; R60 May impair fertility. Repr. Cat. 2; R60 May impair fertility. Repr. Cat. 3; R62 Possible risk of impaired fertility

CLP

Reproductive toxicity Repr. 1A Repr. 1B Repr. 2 H360: May damage fertility or the unborn child <state specific effect if known > <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. H361: Suspected of damaging fertility or the unborn child <state specific effect if known> <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

 

 It is concluded that the Calcium dodecylbenzenesulfonate does not meet the criteria to be classified for human health hazards for Reproductive toxicity