Sodium dodecylbenzenesulfonate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

It is concluded that the substance Sodium 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:

other: published data

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

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 Sodium dodecylbenzenesulfonate (CAS No. 25155-30-0, EC Number; 246-680-4) ) and the dissociated acid it readily dissociates in water and release the dodecylbenzene sulfonic anion in solution.

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:

reproductive performance

Clinical signs:

not examined

Remarks on result:

other: no offspring - no mating - screening study

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 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.

Reference 2

Endpoint:

three-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

other: published data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

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:

other: published data

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

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:

QSAR model,Estrogen Receptor Binding method, relevant for reproductive toxicity endpoints in fish and mammals.

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.

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

Sodium dodecylbenzenesulfonate have a molecular weight of less than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore sodium dodecylbenzenesulfonate does not cause reproductive toxicity.
1.1. CAS number: 25155-30-0
1.2. Other regulatory numbers:
Not reported
1.3. Chemical name(s):
benzenesulfonic acid, dodecyl-, sodium salt
sodium dodecylbenzenesulfonate
sodium 2-dodecylbenzenesulfonate
1.4. Structure codes:
a. SMILES:
CCCCCCCCCCCCc1ccccc1S(=O)(=O)O{-}.[Na]{+}
1.6. Profiling results:
DNA binding by OECD
No alert found
Est rogen Receptor Binding
Non binder, without OH or NH2 group
OECD HPV Chemical Categories
Linear alkylbenzene sulfonates
Protein binding by OECD
No alert found
Protein binding potency
Not possible to classify according to these rules (GSH)
Superfragments
No superfragment
Toxic hazard classification by Cramer (original)
High (Class III)
US-EPA New Chemical Categories
Anionic Surfactants

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:

other: see 'Remark'

Remarks on result:

other: Generation: QSAR model (migrated information)

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

Sodium dodecylbenzenesulfonate have a molecular weight of less than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore sodium dodecylbenzenesulfonate does not cause reproductive toxicity.
1.1. CAS number: 25155-30-0
1.2. Other regulatory numbers:
Not reported
1.3. Chemical name(s):
benzenesulfonic acid, dodecyl-, sodium salt
sodium dodecylbenzenesulfonate
sodium 2-dodecylbenzenesulfonate
1.4. Structure codes:
a. SMILES:
CCCCCCCCCCCCc1ccccc1S(=O)(=O)O{-}.[Na]{+}
1.6. Profiling results:
DNA binding by OECD
No alert found
Est rogen Receptor Binding
Non binder, without OH or NH2 group
OECD HPV Chemical Categories
Linear alkylbenzene sulfonates
Protein binding by OECD
No alert found
Protein binding potency
Not possible to classify according to these rules (GSH)
Superfragments
No superfragment
Toxic hazard classification by Cramer (original)
High (Class III)
US-EPA New Chemical Categories
Anionic Surfactants

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:

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

Remarks on result:

other: Generation: QSAR model

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.

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

Conclusions:

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

Executive summary:

Sodium dodecylbenzenesulfonate  have a molecular weight of less than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore sodium dodecylbenzenesulfonate  does not cause reproductive toxicity.

1.1. CAS number: 25155-30-0

1.2. Other regulatory numbers:

Not reported

1.3. Chemical name(s):

benzenesulfonic acid, dodecyl-, sodium salt

sodium dodecylbenzenesulfonate

sodium 2-dodecylbenzenesulfonate

1.4. Structure codes:

a. SMILES:

CCCCCCCCCCCCc1ccccc1S(=O)(=O)O{-}.[Na]{+}

1.6. Profiling results:

DNA binding by OECD

No alert found

Est rogen Receptor Binding

Non binder, without OH or NH2 group

OECD HPV Chemical Categories

Linear alkylbenzene sulfonates

Protein binding by OECD

No alert found

Protein binding potency

Not possible to classify according to these rules (GSH)

Superfragments

No superfragment

Toxic hazard classification by Cramer (original)

High (Class III)

US-EPA New Chemical Categories

Anionic Surfactants

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

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 Sodium dodecylbenzenesulfonate with regard to reproduction.
It is concluded that the substance Sodium dodecylbenzenesulfonate does not meet the criteria to be classified for human health hazards for 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 Sodium dodecylbenzenesulfonate with regard to Developmental toxicity / teratogenicity 

Link to relevant study records

Reference

Reference 1

Endpoint:

developmental toxicity

Type of information:

other: published data

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

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 Sodium dodecylbenzenesulfonate (CAS No. 25155-30-0, EC Number; 246-680-4) ) and the dissociated acid it readily dissociates in water and release the dodecylbenzene sulfonic anion in solution.

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

Fetal body weight changes:

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.

Remarks on result:

other: Embryotoxic / teratogenic effects:no effects

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:

other: published data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

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.

Reference 3

Endpoint:

developmental toxicity

Type of information:

other: published data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: After overnight mating, the rats were randomly allocated to five groups which included one control group and four different treatment groups. LAS was prepared daily as a series of graded aqueous solutions. Animals in all groups were dosed orally at the standard volume of 1.0 mL/100 g. Control animals were dosed in a similar manner with distilled water used as the vehicle. The dams were observed daily for signs of toxicity and weighed on days 1, 3, 6, 10, 14, 17 and 20 of pregnancy. On day 20, the rats were killed by CO2 euthanasia. Their ovaries and uterine contents were examined immediately for number of corpora lutea, number of viable young, number of resorption sites, litter weight, and fetal abnormalities.

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: Charles River CD strain

Details on test animals or test system and environmental conditions:

Charles River CD strain rat, Female

Route of administration:

other: oral in distilled water

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

day 6 to day 15 of pregnancy

Frequency of treatment:

daily

Duration of test:

20 days

Control animals:

yes, concurrent no treatment

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Parent animals were observed daily. Change in bodyweight was not affected by treatment at 0.2, 2.0, and 300 mg/kg, but treatment at 600 mg/kg was associated with retarded weight gain and a transient diarrhea following initiation of treatment. The pregnancy rate was comparable at all dosages.

Dose descriptor:

NOAEL

Effect level:

300 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
Embryonic and fetal development were assessed by the incidence of major malformations. The incidence of minor visceral anomalies was unaffected by treatment at any dosage. The distribution of skeletal variants were not statistically significant with the exception of a marginal retardation of sternebral ossification at 600 mg/kg.

Dose descriptor:

NOAEL

Effect level:

300 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: teratogenicity

Abnormalities:

not specified

Developmental effects observed:

not specified

Pregnancy/litter data: The litter parameters assessed included litter size, fetal loss and litter weight. These parameters were not significantly affected by any dosage. Mean pup weights were statistically higher at 0.2, 2.0 and 300 mg/kg.

Conclusions:

NOAEL = 300 mg/kg for both maternal and teratogenicity.

Executive summary:

Female rats were given LAS orally in distilled water from gestation days 6 to 15 during pregnancy. Some effects such as decreased weight gain and transient diarrhea occurred at the highest dose. Pregnancy rates were comparable at all doses. Litter parameters were not significantly affected at any dose. No significant differences were observed in visceral anomalies or skeletal variants, with the exception of a marginal retardation of sternabral ossification at the highest dose.

Reference 4

Endpoint:

developmental toxicity

Type of information:

other: published data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: Animals received doses by gavage daily from days 6-15 of gestation. Twenty animals per dose group were used.

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

other: CD

Details on test animals or test system and environmental conditions:

Species/strain: Rat: CD,Sex: Female

Route of administration:

oral: gavage

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

day 6 - 15 of pregnancy

Frequency of treatment:

daily

Duration of test:

sacrifice at day 20 of gestation

No. of animals per sex per dose:

Twenty animals per dose group were used.

Control animals:

yes, concurrent no treatment

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Body weight gain was retarded in the highest dose group from the start of dosing and showed partial recovery toward the end of the dosing period. One animal died in this group but it could not be conclusively related to treatment. The toxic effects were associated with disturbance of the gastrointestinal tract. Pregnancy rate was comparable at all dosages.

Dose descriptor:

NOAEL

Effect level:

300 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
No differences were observed among dose groups and the control group with respect to number of litters, viable young, litter weight, foetal weight, embryonic deaths, implantations, corpora lutea, pre- and post implantation embryonic loss, major malformations, minor visceral or embryonic loss, major malformations, minor visceral or skeletal anomalies or incidence of pups with extra ribs.

Dose descriptor:

NOAEL

Effect level:

600 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: teratogenicity

Abnormalities:

not specified

Developmental effects observed:

not specified

Conclusions:

NOAEL Maternal Toxicity: 300 mg/kg bw
NOAEL teratogenicity: 600 mg/kg bw

Executive summary:

Twenty animals per dose group were used. Animals were daily administered at day 6-15 of pregnancy by gavage with LAS at doses of 0.2, 2, 300, 600 mg/kg bw/day and sacrificed at day 20 of gestation. A control group was used. The body weight gain was retarded in the highest dose group from the start of dosing and showed partial recovery toward the end of the dosing period. One animal died in this group, but it could not be conclusively related to treatment. The toxic effects were associated with disturbance of the gastrointestinal tract. Pregnancy rates were comparable at all dosage.

No differences were observed among the dose groups and the control group with respect to: number of litters, viable young, litter weight, foetal weight, embryonic deaths, implantations, corpora lutea, pre- and post-implantation embryonic loss, major malformations, and minor visceral or skeletal anomalies or incidence of pups with extra ribs.

NOAEL Maternal: 300 mg/kg bw/day

NOAEL teratogenicity: 600 mg/kg bw

Reference 5

Endpoint:

developmental toxicity

Type of information:

other: published data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: The dosage volume was 0.5 mL which was applied to an area of skin (4x4 cm) from which the fur was removed. The nominal doses were 0.6, 6.0, and 60 mg/kg bw d.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

other: CD

Details on test animals or test system and environmental conditions:

Species/strain: Rat: CDSex: Female

Route of administration:

dermal

Details on exposure:

The dosage volume was 0.5 mL which was applied to an area of skin (4x4 cm) from which the fur was removed.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

days 2 through 15 of gestation

Frequency of treatment:

Daily

Duration of test:

days 2 through 15 of gestation

Control animals:

yes, concurrent no treatment

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
At the high dose, local irritation was observed resulting in a slightly lower body weight gain and hypersensitivity (i.e., animals were increasingly irritable).

Dose descriptor:

NOAEL

Effect level:

6 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No differences were observed among the dose groups and the control group with respect to number of litters, viable young, litter weight, foetal weight, embryonic deaths, implantations, corpora lutea, or pre- and post implantation embryonic loss. The incidences of major malformations, minor visceral or skeletal anomalies, and skeletal variants were not different between controls and dose groups even at maternal by toxic doses.

Dose descriptor:

NOAEL

Effect level:

60 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: teratogenicity

Abnormalities:

not specified

Developmental effects observed:

not specified

Pregnant female rats were exposed daily at days 2 through 15 of gestation to LAS at doses of 0.03%, 0.3%, or 3% on the shaved skin as 0.5 ml aqueous solution (0.6, 6, 60 mg/kg bw/day). A control group was used.

Maternal toxicity: at the high dose, local irritation was observed, resulting in a slightly lower body weight gain and hypersensitivity. Teratogenicity: no differences were observed among the dose groups and the control group with respect to: number of litters, viable young, litter weight, foetal weight, embryonic deaths, implantations, corpora lutea, pre- and post implantation embryonic loss. The incidences of major malformations, minor visceral or skeletal anomalies, and skeletal variants were not different between controls and dose groups even at maternal toxic doses.

NOAEL Maternal: 6 mg/kg bw/day

NOAEL Foetuses: 60 mg/kg bw/day

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: 0.3% (6 mg/kg bw d)

NOAEL teratogenicity: 3% (60 mg/kg bw d)

Results:

Maternal toxicity:

At the high dose, local irritation was observed resulting in a slightly lower body weight gain and hypersensitivity (i.e., animals were increasingly irritable).

Teratogenicity:

No differences were observed among the dose groups and the control group with respect to number of litters, viable young, litter weight, foetal weight, embryonic deaths, implantations, corpora lutea, or pre- and post implantation embryonic loss. The incidences of major malformations, minor visceral or skeletal anomalies, and skeletal variants were not different between controls and dose groups even at maternal by toxic doses.

Reference 6

Endpoint:

developmental toxicity

Type of information:

other: published data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: The dosage volume was 0.5 mL which was applied to an area of skin (2 x 3 cm) from which the fur was removed. The nominal doses were 5, 50, and 500 mg/kg bw/day.

GLP compliance:

not specified

Limit test:

no

Species:

mouse

Strain:

CD-1

Details on test animals or test system and environmental conditions:

Species/strain: Mouse/CD-1 Sex: Female

Route of administration:

dermal

Details on exposure:

The dosage volume was 0.5 mL which was applied to an area of skin (2 x 3 cm) from which the fur was removed. The nominal doses were 5, 50, and 500 mg/kg bw/day.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

days 2 through 13 of gestation

Frequency of treatment:

Daily

Duration of test:

days 2 through 13 of gestation

Control animals:

yes, concurrent no treatment

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
At the high dose, severe local irritation was observed resulting in body weight loss and hypersensitivity (i.e., animals were increasingly irritable), which was also observed at the medium dose. The conclusion of the authors was that LAS caused marked toxicity at the high dose and moderate or mild toxicity at the medium dose.

Dose descriptor:

NOAEL

Effect level:

5 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
At the lowest dose, the dose with no maternal toxicity, no differences were observed among the LAS group and the control group with respect to number of litters, viable young, litter weight, foetal weight, embryonic deaths, implantations, corpora lutea, pre- and post implantation embryonic loss. The incidences of major malformations, minor visceral or skeletal anomalies, and skeletal variants were not different between controls and the LAS group.
Maternally toxic dosages were associated with a significantly increased foetal loss and consequent reduction of litter size. This was due almost entirely to total litter losses as values, for the one surviving litter at 3% was similar to the control litters. At the medium dose, the moderate degree of maternal toxicity correlated with a moderate effect on litter values in that, whilst the higher incidence of embryonic deaths differed significantly from control values, the consequent r duction in litter size was not statistically significant.
With regard to major malformations and minor skeletal or visceral anomalies, the assessment of litters was not possible in the highest dose group due to the ow survival. At the low doses, no treatment related increase of the incidences of major malformations and minor skeletal and visceral anomalies were observed.

Dose descriptor:

NOAEL

Effect level:

50 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: teratogenicity

Abnormalities:

not specified

Developmental effects observed:

not specified

Conclusions:

NOAEL Maternal: 0.03% (5 mg/kg bw d)
NOAEL teratogenicity: 0.3% (50 mg/kg bw d)

Executive summary:

Doses of 0.03, 0.3, or 3% LAS (5, 50, and 500 mg/kg bw/day) in aqueous solution were applied daily onto the shaved skin of females mice (days 2 through 13 of gestation). The dosage volume was 0.5 ml, which was applied to an area of skin (2 x 3 cm). Controls groups were used. At the high dose, severe local irritation was observed resulting in body weight loss and hypersensitivity, which was also observed at the medium dose. Teratogenicity: at the lowest dose, the dose with no maternal toxicity, no differences were observed among the LAS group and the control group with respect to: number of litters, viable young, litter weight, foetal weight, embryonic deaths, implantations, corpora lutea, pre- and post-implantation embryonic loss. The incidences of major malformations minor visceral or skeletal anomalies, and skeletal variants were not different between controls and the tested group. Maternally toxic dosages were associated with a significantly increased foetal loss and consequent reduction of litter size. This was due almost entirely to total litter losses, as values for the one surviving litter at the highest dose were similar to the control litters. At the medium dose, the moderate degree of maternal toxicity correlated with a moderate effect on litter values in that, whilst the higher incidence of embryonic deaths differed significantly from control values, the consequent reduction in litter size was not statistically significant. With regard to major malformations and minor skeletal or visceral anomalies, the assessment of litters was not possible in the highest dose group due to the low survival. At the low doses, no treatment related increases of the incidences of major malformations or minor skeletal and visceral anomalies were observed.

 

NOAEL Maternal: 0.03% (5 mg/kg bw d)

NOAEL teratogenicity: 0.3% (50 mg/kg bw d) 

Reference 7

Endpoint:

developmental toxicity

Type of information:

other: published data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: The dosage volume was 10 mL which was applied to an area of skin (12 x 20 cm) from which the fur was removed. The nominal doses were 0.9, 9.0, and 90 mg/kg bw/day. Thirteen rabbits per dose were used.

GLP compliance:

not specified

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Species/strain: rabbit/New Zealand white Sex: Female

Route of administration:

dermal

Details on exposure:

The dosage volume was 10 mL which was applied to an area of skin (12 x 20 cm) from which the fur was removed. The nominal doses were 0.9, 9.0, and 90 mg/kg bw/day. Thirteen rabbits per dose were used.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

17 days (days 1 through 16 of gestation)

Frequency of treatment:

Daily

Duration of test:

17 days (days 1 through 16 of gestation)

No. of animals per sex per dose:

Thirteen rabbits per dose were used.

Control animals:

yes, concurrent no treatment

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
At the high dose, local irritation was observed resulting in body weight loss and hypersensitivity (i.e., animals were increasingly irritable). The medium dose caused retarded body weight gain and hypersensitivity.

Dose descriptor:

NOAEL

Effect level:

0.9 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
At the medium and low dose, no differences were observed among the dose groups and the control group with respect to number of litters, viable young, litter weight, foetal weight, embryonic deaths, implantations, corpora lutea, pre and post implantation embryonic loss. The high dose was associated with slightly, but not significantly, higher foetal loss and lower litter size. The incidences of major malformations, minor visceral or skeletal anomalies, and skeletal variants were not different between controls and dose groups even at maternal toxic doses.

Dose descriptor:

NOAEL

Effect level:

90 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: teratogenicity

Abnormalities:

not specified

Developmental effects observed:

not specified

Conclusions:

NOAEL Maternal: 0.03% (0.9 mg/kg bw d)
NOAEL teratogenicity: 3% (90 mg/kg bw d)

Executive summary:

Female rabbits were exposed (days 1 through 16 of gestation) to aqueous solutions of LAS at 0.03%, 0.3%, or 3% on shaved skin (0.9, 9.0, and 90 mg/kg bw/day).Control groups were present. The dosage volume was 10 ml, which was applied to an area of skin (12 x 20 cm) from which the fur was removed. At the highest dose, local irritation was observed in parental animals, resulting in body weight loss an hypersensitivity. The medium dose caused retarded body weight gain and hypersensitivity. At the medium and low dose, no differences were observed among the dose groups and the control group with respect to: number of litters, viable young, litter weight, foetal weight, embryonic deaths, implantations, corpora lutea, pre- and post-implantation embryonic loss. The high dose was associated with a slightly, but not significantly, higher foetal loss and lower litter size. The incidences of major malformations, minor visceral or skeletal anomalies, and skeletal variants were not different between controls and dose groups even at maternal toxic doses.

NOAEL Maternal: 0.9 mg/kg bw/day

NOAEL Foetuses: 90 mg/kg bw/day, corresponding to the highest dose tested

Reference 8

Endpoint:

developmental toxicity

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 DART QSAR method for chemicals properties assessment.. This method is relevant for Developmental and Reproductive toxicity endpoints in 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 Developmental and Reproductive toxicity. This method is relevant for Developmental and Reproductive toxicity endpoints in mammals.

GLP compliance:

no

Remarks:

not applicable DART QSAR method for chemicals properties assessment..

Limit test:

no

Species:

rat

Strain:

other: QSAR model

Route of administration:

other: QSAR model

Vehicle:

other: QSAR model

Details on exposure:

This grouping method contains simple categories for Developmental and Reproductive toxicity. This method is relevant for Developmental and Reproductive toxicity endpoints in mammals. The database include a set of 716 chemicals (664 positive, 16 negative, and 36 with insufficient data) that have been evaluated for their DART potential. These chemicals were grouped into 25 different categories, and 129 sub-categories, based on defined receptor binding and chemical properties, and when known, their MOA. Data is separated into two types of endpoints: developmental and reproductive toxicity. Detailed information for the effect associated with observed data is available in the metadata information of the database.

Analytical verification of doses or concentrations:

no

Details on mating procedure:

QSAR model

Duration of treatment / exposure:

QSAR model

Frequency of treatment:

QSAR model

Duration of test:

QSAR model

Control animals:

other: QSAR model

Maternal examinations:

This grouping method contains simple categories for Developmental and Reproductive toxicity. This method is relevant for Developmental and Reproductive toxicity endpoints in mammals. The database include a set of 716 chemicals (664 positive, 16 negative, and 36 with insufficient data) that have been evaluated for their DART potential. These chemicals were grouped into 25 different categories, and 129 sub-categories, based on defined receptor binding and chemical properties, and when known, their MOA. Data is separated into two types of endpoints: developmental and reproductive toxicity. Detailed information for the effect associated with observed data is available in the metadata information of the database.

Fetal examinations:

This grouping method contains simple categories for Developmental and Reproductive toxicity. This method is relevant for Developmental and Reproductive toxicity endpoints in mammals. The database include a set of 716 chemicals (664 positive, 16 negative, and 36 with insufficient data) that have been evaluated for their DART potential. These chemicals were grouped into 25 different categories, and 129 sub-categories, based on defined receptor binding and chemical properties, and when known, their MOA. Data is separated into two types of endpoints: developmental and reproductive toxicity. Detailed information for the effect associated with observed data is available in the metadata information of the database.

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
No adverse effects on the highest dose tested according the DART QSAR method for chemicals properties assessment..
This grouping method contains simple categories for Developmental and Reproductive toxicity. This method is relevant for Developmental and Reproductive toxicity endpoints in mammals. The database include a set of 716 chemicals (664 positive, 16 negative, and 36 with insufficient data) that have been evaluated for their DART potential.

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Fetal body weight changes:

no effects observed

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Basis for effect level:

other: Embryotoxic / teratogenic effects:no effects

Remarks on result:

other: No adverse effects on the highest dose tested according the DART QSAR method for chemicals properties assessment.. This method is relevant for Developmental and Reproductive toxicity endpoints in mammals.

Abnormalities:

not specified

Developmental effects observed:

not specified

See attached QSAR study report

Conclusions:

NOAEL for developmental toxicity was 300 mg/kg bw/day (No adverse effects on the highest dose tested) for sodium dodecylbenzenesulfonate and does not cause developmental toxicity.
Developmental & Reproductive Toxicity (DART): Not known precedent reproductive and developmental toxic potential (DART scheme v.1.0)

Executive summary:

Profiling results:

DNA binding by OECD: No alert found

Est rogen Receptor Binding :Non binder, non cyclic structure

OECD HPV Chemical Categories \;Not categorized

Developmental & Reproductive Toxicity (DART): Not known precedent reproductive and developmental toxic potential (DART scheme v.1.0)

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

Link to relevant study records

Reference

Reference 1

Endpoint:

toxicity to reproduction: other studies

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reference 2

Endpoint:

toxicity to reproduction: other studies

Type of information:

other: published data

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: LAS was injected at doses of 20 mL/kg/day from day 0 to 3 or day 8 to 11 of pregnancy. There were 12 - 19 mice in each treatment group.

GLP compliance:

not specified

Type of method:

in vivo

Species:

mouse

Strain:

ICR

Sex:

female

Details on test animals or test system and environmental conditions:

Species/strain: mouse/ICR Sex: Female

Route of administration:

subcutaneous

Vehicle:

water

Details on exposure:

Subcutaneous injection,Doses: 0.35, 1% in water (20, 200 mg/kg bw d).
LAS was injected at doses of 20 mL/kg/day from day 0 to 3 or day 8 to 11 of pregnancy. There were 12 - 19 mice in each treatment group.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Day 0 to 3 or day 8 to 11 of pregnancy

Frequency of treatment:

daily

Duration of test:

Day 0 to 3 or day 8 to 11 of pregnancy

Remarks:

Doses / Concentrations:
0.35, 1% in water (20, 200 mg/kg bw d)
Basis:
nominal conc.

No. of animals per sex per dose:

12 - 19 mice in each treatment group.

Control animals:

yes, concurrent no treatment

Details on study design:

LAS was injected at doses of 20 mL/kg/day from day 0 to 3 or day 8 to 11 of pregnancy.

Dose descriptor:

NOAEL

Remarks:

Maternal

Effect level:

20 mg/kg bw/day

Based on:

test mat.

Sex:

female

Basis for effect level:

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

Dose descriptor:

NOAEL

Remarks:

teratogenicity

Effect level:

200 mg/kg bw/day

Based on:

test mat.

Sex:

female

Basis for effect level:

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

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.

Conclusions:

NOAEL Maternal: 0.35% (20 mg/kg bw d)
NOAEL teratogenicity : 1% (200 mg/kg bw d)
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.

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 Sodium dodecylbenzenesulfonate in section 2.1 and 2.2. in IUCLID 5.4., 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 Sodium dodecylbenzenesulfonate does not meet the criteria to be classified for human health hazards for Reproductive toxicity