Dodecylbenzenesulphonic acid

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

It is concluded that the substance Dodecylbenzenesulphonic acid/Dodecylbenzenesulfonic acid  does not meet the criteria to be classified for human health hazards for Reproductive toxicity

Link to relevant study records

Reference

Endpoint:

fertility, other

Remarks:

based on test type

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

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

Generation:

F1

Based on:

test mat.

Remarks on result:

not measured/tested

Reproductive effects observed:

not specified

Conclusions:

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

Executive summary:

Effects on Fertility

In reproductive toxicity study performed according to the reproduction/developmental toxicity screening test [OECD TG 422] conditions and dose were same 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.

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 Dodecylbenzenesulphonic acid/ Dodecylbenzenesulfonic acid with regard to reproduction.
It is concluded that the substance Dodecylbenzenesulphonic acid/ Dodecylbenzenesulfonic acid 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  Dodecylbenzenesulphonic acid/ Dodecylbenzenesulfonic acid  with regard to Developmental toxicity / teratogenicity 

Link to relevant study records

Reference

Reference 1

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

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 (incl. QA statement)

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

Clinical signs:

no effects observed

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

Other effects:

no effects observed

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

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

Dose descriptor:

NOAEL

Effect level:

400 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Embryotoxic / teratogenic effects:no effects

Remarks on result:

other: statistically significant decrease in corpora lutea was observed in the 400 mg/kg bw/day group.

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.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

400 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

17.4 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

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

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

20 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

Oral exposure

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

NOAELrat  = 400 mg/kg bw/day

Dermal exposure:

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

Results:

Maternal toxicity:

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

Teratogenicity:

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

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

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

Inhalation exposure:

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

NOAEL rat             

 400 mg/kg bw/day

÷1.15 m3/kgbw

÷20m3/rat

NOAECrat    17.4 mg/m3

Toxicity to reproduction: other studies

Additional information

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

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

 

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

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

 

Justification for classification or non-classification

Based on the hazard assessment of  Dodecylbenzenesulphonic acid/ Dodecylbenzenesulfonic acid in section 2.1 and 2.2. in IUCLID 6, available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health” and according 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 substance  Dodecylbenzenesulphonic acid/ Dodecylbenzenesulfonic acid does not meet the criteria to be classified for human health hazards for Reproductive toxicity