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Description of key information

Oral repeated dose toxicity 
Repeated oral dosing of dodecylbenzenesulfonic acid (as a read across for Calcium dodecylbenzenesulfonate ) resulted in soft feces, and squamous cell hyperplasia of stomach in both sexes, and liquid feces and soled perineal region, a decrease in body weight and food consumption, forestomach erosion/ulcer in males at 400 mg/kg bw/day, and squamous cell hyperplasia of stomach in both sexes at 200 mg/kg bw/day. Based on results, all findings were completely or partially reversed during the 15 days recovery period. The target organ for oral dosing of dodecylbenzenesulfonic acid was considered as stomach.
The NOAEL and the LOAEL for repeated toxicity of Calcium dodecylbenzenesulfonate was considered to be 100 mg/kg bw/day and 200 mg/kg bw/day in both sexes, respectively.
Dermal repeated dose toxicity
LAS (as a read across) was applied for 15 days to the backs of male rats, at daily doses of 0.5 g of solutions at 20 and 30% (about 286 and 427 mg/kg bw/day).
Histological examinations of the application site revealed severe necrosis of the region from the epidermis cuticle to the upper layer of the dermis, severe infiltration of leukocytes in the necrotic site, and diffuse inflammatory cell infiltration of all layers of the corium. The effects on body weight are to be considered related to the LAS irritation.
The LOAEL for these effects is 286 mg/kg bw/day, the lower dose tested.
The NOAEL for these effects is<286 mg/kg bw/day.
Inhalation repeated dose toxicity
There are no Inhalation repeated 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
100 mg/kg bw/day
÷1.15 m3/kgbw
÷20m3/rat
NOAECrat - 4.35 mg/m3

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Dodecylbenzene sulfonic acids (CAS# 27176-87-0 , EC Number; 248-289-4) ) is a very close analogue of Calcium dodecylbenzenesulfonate (CAS No 26264-06-2, EC Number;247-557-8) ) and the dissociated acid it readily dissociates in water and release the dodecylbenzene sulfonic anion in solution.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
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
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:
0, 100, 200, and 400 mg/kg bw/day (Dosing volume 10ml/kg/day)
Basis:
nominal in diet
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:
- 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
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:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Details on results:
-Clinical signs: Treatment-related clinical signs such as salivation and soft feces were observed in all males of the 400 mg/kg bw/day group during the premating and mating periods. Soiled perineal and liquid feces were observed in 2 males of 400 mg/kg bw/day group during the premating. Salivation and soft feces were observed in 9 and 8 females during the premating and in 8 and 5 during the mating period in the 400 mg/kg bw/day group, respectively. Thin appearance, salivation, staining around mouth, soiled perineal region and soft feces were observed in 1, 10, 1, 1 and 4 females during the gestation period in the 400 mg/kg group, respectively. Thin appearance and salivation were observed in 1 and 10 animals in the 400 mg/kg bw/day group during the lactation period, respectively.

- Body weights and food consumption: In males, a statistically significant decrease was observed on days 8 and 14 of premating. In females, there was no statistically significant changes except a decrease on day 20 of gestation at 400 mg/kg bw/day. In males, a statistically significant decrease in food consumption was observed in the 400 mg/kg bw/day group on days 2 and 9 of the premating, and in females it was observed on day 2 of premating and day 8 of gestation.

- Neurobehavioral evaluation: No treatment-related changes were observed in any of the treatment group.- Urinalysis for males: There were no treatment-related changes for males.

- Hematological test : In hematology test, activated partial thromboplastin time (APTT) was statistically significantly decreased in male of the 400 mg/kg bw/day group. No treatment-related changes were observed in females. In recovery group, a statically significant decrease in RBC count (RBC) was observed in males of the 400 mg/kg bw/day group and an increase in mean corpuscular hemoglobin (MCH) was observed in females.

- Biochemical test: In serum biochemistry test, a statistically significant increase in A/G ratio andalanine aminotransferase (ALT) was observed in males of the 400 mg/kg bw/day group. In females, a statistically significant decrease in blood urine nitrogen (BUN) observed in all treatment groups and an decrease in albumin (ALB) was also observed in the 400 mg/kg bw/day group. In recovery group, a statistically significant decrease in ALT and increase in ALP were observed in females of the 400 mg/kg bw/day group.

- Gross findings: There were no treatment-related changes for all animals

- Organ weights: In males, no a statistically significant changes were observed in any of the treatment groups. In females, a statistically significant increase in absolute weight of ovaries was observed in the 200 mg/kg bw/day group, and a decrease in absolute weight of salivary gland and heart was observed in the 400 mg/kg bw/day groups. The mean weight of ovaries for main group was 0.108 g in compared with vehicle control of 0.093 g and the mean weight of salivary glands for main group was 0.462 g in compared with vehicle control of 0.532 g. Also, the mean weight of heart for main group was 0.816 g in compared with vehicle control of 0.955 g. In recovery groups, a significant decrease in liver and kidney was observed in males the 400 mg/kg bw/day group. No significant differences were observed between vehicle control and test group for organ weights in females.

- Histopathological findings: Squamous cell hyperplasia in stomach was observed in males and females at 200 and 400 mg/kg bw/day. Two cases of minimal forestomach erosion/ulcer were also observed in males at 400 mg/kg bw/day.
Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Dose descriptor:
LOAEL
Effect level:
200 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Critical effects observed:
not specified
Conclusions:
Oral administration of dodecylbenzenesulfonic acid to rats resulted in soft feces, and squamous cell hyperplasia of stomach in both sexes at 400mg/kg bw/day, and liquid feces and soled perineal region, a decrease in body weight and food consumption in males at 400 mg/kg bw/day. In hematology examination, squamous cell hyperplasia of stomach was observed in both sexes at 200 mg/kg bw/day and forestomach erosion/ulcer was observed in males at 400mg/kg bw/day. Based on these effects the NOAEL value was 100 mg/kg bw/day for male and female rats and the LOAEL value was 200 mg/kg bw/day for male and female rats. From these results, the target organ for oral dosing of dodecylbenzenesulfonic acid was considered to be the stomach.
Executive summary:

Repeated oral dosing of dodecylbenzenesulfonic acid resulted in soft feces, and squamous cell hyperplasia of stomach in both sexes, and liquid feces and soled perineal region, a decrease in body weight and food consumption, forestomach erosion/ulcer in males at 400 mg/kgbw/day, and squamous cell hyperplasia of stomach in both sexes at 200 mg/kgbw/day.Also,activated partial thromboplastin time (APTT) was statistically significantly decreased in male of the 400 mg/kg bw/day group. Inserum biochemistry test, a statistically significant increase in A/G ratio and alanine aminotransferase (ALT) was observed in males of the 400 mg/kg bw/day group.As a result of organ weight test, no a statistically significant changes were observed in any of the treatment groups in males. A statistically significant increase in absolute weight of ovaries was observed in the 200 mg/kg bw/day group, and a decrease in absolute weight of salivary gland and heart was observed in the 400 mg/kg bw/day groups.

Based on results, all findings were completely or partially reversed during the15daysrecovery period. The target organ for oral dosing of dodecylbenzenesulfonic acid was considered as stomach. The NOAEL and the LOAEL for repeated toxicity of dodecylbenzenesulfonic acid was considered to be 100 mg/kg bw/day and 200 mg/kg bw/day in both sexes, respectively.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
4.35 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
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
100 mg/kg bw/day
÷1.15 m3/kgbw
÷20m3/rat
NOAECrat 4.35 mg/m3

Repeated dose toxicity: inhalation - local effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
4.35 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
Inhalation exposure:
There are no Inhalation Repeated 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
100 mg/kg bw/day
÷1.15 m3/kgbw
÷20m3/rat
NOAECrat 4.35 mg/m3

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
C12 LAS; Linear Alkylbenzene Sulfonate (LAS)) is a very close analogue of Calcium dodecylbenzenesulfonate (CAS No 26264-06-2, EC Number; 247-557-8) ) and read-across is valid.
Reason / purpose for cross-reference:
read-across source
Qualifier:
no guideline followed
Principles of method if other than guideline:
LAS was applied to the backs of the rats. On the 16th day of the experiment, skin at the application site and the tissues of the tongue and oral mucosa (to examine the effects of licking) of the rats that received 30% were examined histologically
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Type of coverage:
occlusive
Vehicle:
other: distilled water
Details on exposure:
LAS was applied for 15 days to the backs of male rats, at daily doses of 0.5 g of solutions at 20 and 30% (about 286 and 427 mg/kg bw/day).
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
15 days
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
286 and 427 mg/kg bw day
Basis:
nominal per unit body weight
Control animals:
yes
Details on study design:
LAS was applied for 15 days to the backs of male rats, at daily doses of 0.5 g of solutions at 20 and 30% (about 286 and 427 mg/kg bw/day). On the 16th day of the experiment, the animals were assessed. Body weight gain was suppressed in the 20% group (286 mg/kg bw/day) and the body weight was decreased in the 30% group (427 mg/kg bw/day). An infiltrating, yellowish-reddish brown crust was observed after 2-3 days in the lower dose group, and after 1-2 days in the high dose group. After 4-6 days the crust was abraded and erosion occurred at the abraded site.
Sacrifice and pathology:
On the 16th day of the experiment, skin at the application site and the tissues of the tongue and oral mucosa (to examine the effects of licking) of the rats that received 30% were examined histologically
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Ophthalmological findings:
not examined
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Details on results:
Body weight gain was suppressed in the 20% group (286 mg/kg bw/day) and the body weight was decreased in the 30% group (427 mg/kg bw/day). An infiltrating, yellowish-reddish brown crust was observed after 2-3 days in the lower dose group, and after 1-2 days in the high dose group. After 4-6 days the crust was abraded and erosion occurred at the abraded site.
Histological examinations of the application site revealed severe necrosis of the region from the epidermis cuticle to the upper layer of the dermis, severe infiltration of leukocytes in the necrotic site, and diffuse inflammatory cell infiltration of all layers of the corium.
The effects on body weight are to be considered related to the LAS irritation.
Dose descriptor:
NOAEL
Effect level:
< 286 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
body weight and weight gain
clinical signs
histopathology: non-neoplastic
mortality
Dose descriptor:
LOAEL
Effect level:
286 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
body weight and weight gain
clinical signs
histopathology: non-neoplastic
mortality
Critical effects observed:
not specified
Conclusions:
The LOAEL for body weight effects is 286 mg/kg bw/day, the lower dose tested.
The NOAEL for body weight effects is <286 mg/kg bw/day.
Executive summary:

LAS was applied for 15 days to the backs of male rats, at daily doses of 0.5 g of solutions at 20 and 30% (about 286 and 427 mg/kg bw/day). On the 16thday of the experiment, the animals were assessed. Body weight gain was suppressed in the 20% group (286 mg/kg bw/day) and the body weight was decreased in the 30% group (427 mg/kg bw/day). An infiltrating, yellowish-reddish brown crust was observed after 2-3 days in the lower dose group, and after 1-2 days in the high dose group. After 4-6 days the crust was abraded and erosion occurred at the abraded site. Histological examinations of the application site revealed severe necrosis of the region from the epidermis cuticle to the upper layer of the dermis, severe infiltration of leukocytes in the necrotic site, and diffuse inflammatory cell infiltration of all layers of the corium. The effects on body weight are to be considered related to the LAS irritation.

The LOAEL for these effects is 286 mg/kg bw/day, the lower dose tested.

The NOAEL for these effects is<286 mg/kg bw/day.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
286 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: dermal - local effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
C12 LAS; Linear Alkylbenzene Sulfonate (LAS)) is a very close analogue of Calcium dodecylbenzenesulfonate (CAS No 26264-06-2, EC Number; 247-557-8) ) and read-across is valid.
Reason / purpose for cross-reference:
read-across source
Qualifier:
no guideline followed
Principles of method if other than guideline:
LAS was applied to the backs of the rats. On the 16th day of the experiment, skin at the application site and the tissues of the tongue and oral mucosa (to examine the effects of licking) of the rats that received 30% were examined histologically
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Type of coverage:
occlusive
Vehicle:
other: distilled water
Details on exposure:
LAS was applied for 15 days to the backs of male rats, at daily doses of 0.5 g of solutions at 20 and 30% (about 286 and 427 mg/kg bw/day).
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
15 days
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
286 and 427 mg/kg bw day
Basis:
nominal per unit body weight
Control animals:
yes
Details on study design:
LAS was applied for 15 days to the backs of male rats, at daily doses of 0.5 g of solutions at 20 and 30% (about 286 and 427 mg/kg bw/day). On the 16th day of the experiment, the animals were assessed. Body weight gain was suppressed in the 20% group (286 mg/kg bw/day) and the body weight was decreased in the 30% group (427 mg/kg bw/day). An infiltrating, yellowish-reddish brown crust was observed after 2-3 days in the lower dose group, and after 1-2 days in the high dose group. After 4-6 days the crust was abraded and erosion occurred at the abraded site.
Sacrifice and pathology:
On the 16th day of the experiment, skin at the application site and the tissues of the tongue and oral mucosa (to examine the effects of licking) of the rats that received 30% were examined histologically
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Ophthalmological findings:
not examined
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Details on results:
Body weight gain was suppressed in the 20% group (286 mg/kg bw/day) and the body weight was decreased in the 30% group (427 mg/kg bw/day). An infiltrating, yellowish-reddish brown crust was observed after 2-3 days in the lower dose group, and after 1-2 days in the high dose group. After 4-6 days the crust was abraded and erosion occurred at the abraded site.
Histological examinations of the application site revealed severe necrosis of the region from the epidermis cuticle to the upper layer of the dermis, severe infiltration of leukocytes in the necrotic site, and diffuse inflammatory cell infiltration of all layers of the corium.
The effects on body weight are to be considered related to the LAS irritation.
Dose descriptor:
NOAEL
Effect level:
< 286 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
body weight and weight gain
clinical signs
histopathology: non-neoplastic
mortality
Dose descriptor:
LOAEL
Effect level:
286 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
body weight and weight gain
clinical signs
histopathology: non-neoplastic
mortality
Critical effects observed:
not specified
Conclusions:
The LOAEL for body weight effects is 286 mg/kg bw/day, the lower dose tested.
The NOAEL for body weight effects is <286 mg/kg bw/day.
Executive summary:

LAS was applied for 15 days to the backs of male rats, at daily doses of 0.5 g of solutions at 20 and 30% (about 286 and 427 mg/kg bw/day). On the 16thday of the experiment, the animals were assessed. Body weight gain was suppressed in the 20% group (286 mg/kg bw/day) and the body weight was decreased in the 30% group (427 mg/kg bw/day). An infiltrating, yellowish-reddish brown crust was observed after 2-3 days in the lower dose group, and after 1-2 days in the high dose group. After 4-6 days the crust was abraded and erosion occurred at the abraded site. Histological examinations of the application site revealed severe necrosis of the region from the epidermis cuticle to the upper layer of the dermis, severe infiltration of leukocytes in the necrotic site, and diffuse inflammatory cell infiltration of all layers of the corium. The effects on body weight are to be considered related to the LAS irritation.

The LOAEL for these effects is 286 mg/kg bw/day, the lower dose tested.

The NOAEL for these effects is<286 mg/kg bw/day.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1.6 mg/cm²
Study duration:
subacute
Species:
rat

Additional information

Oral repeated dose toxicity

Oral administration of dodecylbenzenesulfonic acid (as a read across for Calcium dodecylbenzenesulfonate) to rats resulted in soft feces, and squamous cell hyperplasia of stomach in both sexes at 400 mg/kg bw/day, and liquid feces and soled perineal region, a decrease in body weight and food consumption in males at 400 mg/kg bw/day. In hematology examination, squamous cell hyperplasia of stomach was observed in both sexes at 200 mg/kg bw/day and forestomach erosion/ulcer was observed in males at 400mg/kg bw/day. Based on these effects the NOAEL value was 100 mg/kg bw/day for male and female rats and the LOAEL value was 200 mg/kg bw/day for male and female rats.

From these results, the target organ for oral dosing of dodecylbenzenesulfonic acid (as a read across for Calcium dodecylbenzenesulfonate) was considered to be the stomach.

NOAEL -100 mg/kg bw/day for male and female rats.

 

Dermal repeated dose toxicity

 

LAS (as a read across) was applied for 15 days to the backs of male rats, at daily doses of 0.5 g of solutions at 20 and 30% (about 286 and 427 mg/kg bw/day). On the 16thday of the experiment, the animals were assessed. Body weight gain was suppressed in the 20% group (286 mg/kg bw/day) and the body weight was decreased in the 30% group (427 mg/kg bw/day). An infiltrating, yellowish-reddish brown crust was observed after 2-3 days in the lower dose group, and after 1-2 days in the high dose group. After 4-6 days the crust was abraded and erosion occurred at the abraded site. Histological examinations of the application site revealed severe necrosis of the region from the epidermis cuticle to the upper layer of the dermis, severe infiltration of leukocytes in the necrotic site, and diffuse inflammatory cell infiltration of all layers of the corium. The effects on body weight are to be considered related to the LAS irritation.

The LOAEL for these effects is 286 mg/kg bw/day, the lower dose tested.

The NOAELfor these effects is<286mg/kg bw/day.

 

 

Inhalation repeated dose toxicity

There are no Inhalation repeated 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             

100 mg/kg bw/day

÷1.15 m3/kgbw

÷20m3/rat

NOAECrat -  4.35 mg/m3

 


Justification for selection of repeated dose toxicity dermal - local effects endpoint:
The generic modification from the NOAELtest (in mg/kg of body weight) to NOAELmodified (in mg/cm2/day) will be
NOAELin mg/cm2 = ((dose in mg/kg bw)x (average animal weight in kg)) / Treated surface in cm2)
NOAELtest* 0.25/44.5= NOAELmodified

The highest dose not causing irritation/corrosion was 286 mg/kg bw in dermal toxicity study in rats of Sadai, M. and Mizuno, N. 1972.
the modified dose descriptor would be
NOAELmodified =286 mg/kg*0.25 kg/44.5cm2=1.6 mg/cm2

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: stomach; other: all gross lesions and masses

Repeated dose toxicity: inhalation - systemic effects (target organ) digestive: stomach; other: all gross lesions and masses

Repeated dose toxicity: dermal - systemic effects (target organ) other: all gross lesions and masses

Justification for classification or non-classification

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

 

Directive 67/548

Repeated dose toxicity

R33 Danger of cumulative effects.

T; R48/23 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation.

T; R48/23/24 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation and in contact with skin.

T; R48/23/24/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed.

T; R48/23/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed.

T; R48/24 Toxic; Toxic: danger of serious damage to health by prolonged exposure in contact with skin.

T; R48/24/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure in contact with skin and if swallowed.

T; R48/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure if swallowed.

Xn; R48/20 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation.

Xn; R48/20/21 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation and in contact with skin.

Xn; R48/20/21/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed.

Xn; R48/20/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation and if swallowed.

Xn; R48/21 Harmful; Harmful: danger of serious damage to health by prolonged exposure in contact with skin.

Xn; R48/21/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure in contact with skin and if swallowed.

Xn; R48/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure if swallowed.

 

CLP

Repeated dose toxicity

STOT Rep. Exp. 1

STOT Rep. Exp. 2

H372: Causes damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

H373: May cause damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

 

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