Ethylbenzenesulphonic acid

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

The NOAEL was estimated to be 1179.5 mg/kg bw when rats were orally exposed with Ethylbenzenesulphonic acid. 

Thus, as per criteria of CLP regulation, Ethylbenzenesulphonic acid can be Not classified for reproductive toxicity. 

Link to relevant study records

Reference

Endpoint:

toxicity to reproduction

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

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 limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Limit test:

no

Specific details on test material used for the study:

- Name: Ethylbenzenesulphonic acid
- Molecular Weight: 186.23 g/mole
- Molecular Formula: C8H10O3S
- InChI:1S/C8H10O3S/c1-2-7-3-5-8(6-4-7)12(9,10)11/h3-6H,2H2,1H3,(H,9,10,11)
- SMILES:CCc1ccccc1S(O)(=O)=O

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: feed

Type of inhalation exposure (if applicable):

not specified

Vehicle:

unchanged (no vehicle)

Details on exposure:

not specified

Details on mating procedure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

not specified

Frequency of treatment:

not specified

Details on study schedule:

not specified

Dose / conc.:

1 179.5 mg/kg bw/day

No. of animals per sex per dose:

10 males and 10 females

Control animals:

yes, plain diet

Details on study design:

not specified

Positive control:

not specified

Parental animals: Observations and examinations:

not specified

Oestrous cyclicity (parental animals):

not specified

Sperm parameters (parental animals):

not specified

Litter observations:

not specified

Postmortem examinations (parental animals):

not specified

Postmortem examinations (offspring):

not specified

Statistics:

not specified

Reproductive indices:

not specified

Offspring viability indices:

not specified

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

no effects observed

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Dose descriptor:

NOAEL

Effect level:

1 179.5 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

body weight and weight gain

food consumption and compound intake

reproductive performance

other: No effect observed

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Other effects:

not specified

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Dose descriptor:

other: not specified

Generation:

other: not specified

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Dose descriptor:

other: not specified

Generation:

other: not specified

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Reproductive effects observed:

not specified

Treatment related:

not specified

Relation to other toxic effects:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" or "b" or "c" or "d" or "e" or "f" )  and "g" )  and ("h" and ( not "i") )  )  and "j" )  and "k" )  and ("l" and ( not "m") )  )  and "n" )  and ("o" and "p" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Linear alkylbenzene sulfonates by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Anionic Surfactants by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aromatic compound OR Sulfonic acid OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] OR Hydroxy, sulfur attach [-OH] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Suflur {v+4} or {v+6} OR Sulfinic acid [-S(=O)OH] OR Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Alkyl arenes OR Overlapping groups OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Alkyl arenes OR Aryl OR Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Vinyl pyridines by DPRA Cysteine peptide depletion

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Low (Class I) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aliphatic acids and (Met)acrylic acids by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.39

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.77

Conclusions:

The NOAEL was estimated to be 1179.5 mg/kg bw when rats were orally exposed with Ethylbenzenesulphonic acid.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for Ethylbenzenesulphonic acid. The NOAEL was estimated to be 1179.5 mg/kg bw when rats were orally exposed with Ethylbenzenesulphonic acid. 

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 179.5 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Reproductive toxicity:

In different studies, Ethylbenzenesulphonic acid has been investigated for reproductive oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for Ethylbenzenesulphonic acid along with the study available on structurally similar read across substance Amino-5-methylbenzenesulfonic acid (CAS no 88-44-8) and 4-Methylbenzenesulfonyl chloride (CAS 98-59-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for Ethylbenzenesulphonic acid. The NOAEL was estimated to be 1179.5 mg/kg bw when rats were orally exposed with Ethylbenzenesulphonic acid. 

In another experimental study conducted byJ-check (Ministry of Health, Labour and Welfare", "Ministry of the Environment" and "National Institute of Technology and Evaluation, J-check- 2010) on structurally similar read across substance Amino-5-methylbenzenesulfonic acid (CAS no 88-44-8),  Crj:CD(SD) male and female rat were treated with 2-Amino-5-methylbenzenesulfonic acid in the concentration of 0 (vehicle), 100, 300, 1000 mg/kg/day orally by gavage in sesame oil for male consecutive 48 days of 14 days before mating and 14 days of mating period and 20 days after the end of the mating period. and for female administration period was 14 days before the mating and during the mating period (maximum 14 days) and through 3 days of postpartum feeding (41 to 46 days) throughout the gestation period of the female. The females who did not deliver after copulation establishment were for 41 and 43 days up to the day before dissection on 25th gestation. Females that failed to mate were consecutive 48 days of 20 days after the mating period. No mortality was observed in treated male and female rats as compared to control. In male rats, 1 ocular secretion in the 100 mg / kg group of male, 1 hair loss in the 300 mg / kg group, 1 in the 1000 mg / kg group Crust and hair loss were observed in one case and in females, hair removal was observed in the 100 mg / kg group through pregnancy and nursing periods. In male, no effect on body weight and in female at 100 and 1000 mg / kg, statistically significant decrease in body weight were observed only on the 4th day of nursing compared to the control group. However, since there was no obvious difference on the other measurement day and it was a change only for 1 day, and since there was no obvious change in body weight gain during the nursing period, the influence of administration of the test substance It was not thought to be an accidental change. In male rats at 1000 mg/kg bw, statistically significant increase in daily food intake for the 8 to 15 days and the cumulative food consumption from 1 to 15 days and in female rats, no effect on food consumption was observed as compared to control. Similarly, No reproductive effect on copulation, implantation and sexual cycle, gestation length, number of corpora lutea or implantations, implantation index, gestation index, delivery index, purturition or maternal behavior, numbers of offspring or live offspring, sex ratio and live birth index were observed in treated rats as compared to control. At 300 and 1000 mg/kg bw, statistically significant decrease in absolute epididymis weight were observed but no relative weight change and no effect on testicular weight were observed in treated male rats as compared to control. No gross pathological changes were attributed to the administration of the test substance. At 1000 mg/kg bw, cell infiltration of the epididymis, case in skin erosion and squamous cell epithelial hyperplasia , 1 atrophy of the thymus, 1 lung inflammation, 1 stomach ulcer and 1 part of the adrenal cortex one hypertrophy were observed in male rats. At 300 mg/kg bw, seminiferous tubular atrophy of the testes, pulmonary inflammation, 1 case in the liver necrosis and 1 atrophy of the thymus were observed in male rats. At 100 mg/kg bw, 1 Young yolk sac cysts in females who spontaneously delivered, so it was considered that there was no effect on the ovaries of the test substances. 1 Skin inflammatory infiltration and squamous epithelial hyperplasia were observed. In males and females who did not mate, seminiferous tubular atrophy of the testes was observed in males. No abnormal findings were observed in females. No abnormal findings were observed in males who did not establish pregnancy and infertile females. Atrophy of the thymus and purulent inflammation of the uterus were observed in one case in all the dead animals. No abnormal finding was observed in the other case. In addition,No effect on Viability and body weight of neonates were observed on day 0 and 4 andnoclinical sign were observed inneonates as compared to control.No abnormal findings were observed in females. At autopsy on 4th day of nursing, in the male, thymus neck remnant was 1 in the control group, 1 in the renal pelvic enlargement in the 300 mg / kg group, in the female in the control group and in the 300 mg / kg group in the renal pelvic enlargement in the kidney It was recognized in 1 and 3 cases respectively. In both cases, expression was expressed in a few cases, which was not related to administration of the test substance. Therefore, NOAEL was considered to be 1000 mg/kg/day for P and F1 generation when male and female rats treated with 2-Amino-5-methylbenzenesulfonic acid orally by gavage for approx 68 days.

Further supported by experimental study given by OECD SIDS (Korea National Institute of Environmental Research peer reviewed, OECD SIDS, August 2004) on structurally similar read across substance 4-Methylbenzenesulfonyl chloride (CAS 98-59-9),male and female rat were treated with 4-Methylbenzenesulfonyl chloride in the concentration of 0, 150, 350 and 750 mg/kg bw/day orally by gavage in sesame oil for male consecutive 35 days and for female 36 ~ 51 days. In male rats, intermittent (blood-like) salivation and staining around mouth were observed at 150 mg/kg bw and in females, intermittent (blood-like) salivation, staining around mouth and irregular respiration were observed. Similarly, difficult delivery and poor nursing were observed in treated female rats at 150 mg/kg bw. But, no effect observed on Reproductive performance at 350 and 750 mg/kg bw. In addition,NoClinical sign were observed inpups.Therefore, NOAEL was considered to be 750 mg/kg/day for P and F1 generation when male and female rats treated with4-Methylbenzenesulfonyl chlorideorally by gavage for 36 ~ 51 days.

Thus, based on the above study and predictions on Ethylbenzenesulphonic acid and its read across substances, it can be concluded that NOAEL value is 1179.5 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, Ethylbenzenesulphonic acid can be Not classified for reproductive toxicity. 

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the above study and predictions on Ethylbenzenesulphonic acid and its read across substances, it can be concluded that NOAEL value is 1179.5 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, Ethylbenzenesulphonic acid can be Not classified for reproductive toxicity.