Benzene, mono-C10-14-alkyl derivs., fractionation bottoms, intermediate cut, sulfonated, sodium salts

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

two-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

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

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study meets the criteria for Klimisch code 1, as it is conducted to OECD guidelines and to GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]

Deviations:

no

GLP compliance:

yes

Species:

rat

Strain:

Sprague-Dawley

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;
- 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:

oral: gavage

Vehicle:

corn oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: Corn oil was added to the test substance to achieve the desired volume and then stirred for 30 minutes.


VEHICLE
- Justification for use and choice of vehicle (if other than water): Corn oil

Details on mating procedure:

- M/F ratio per cage: 1:1
- Length of cohabitation:
- Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged individually

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

F0 males - 70 days premating; mating period through completion of parturition
F0 females - 14 days premating; mating; 25 days of gestation and 20 days of lactation.
F1 pups - gestation through day 20 of lactation

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
0, 50, 167, 500 mg/kg bw
Basis:
other: gavage

No. of animals per sex per dose:

28 F0 rats/sex/group in control, low, mid and high dose

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: Based on results of a 28 day oral gavage study.

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly and daily for females during gestation


BODY WEIGHT: Yes
- Time schedule for examinations: Weekly and on the day on euthanasia for males. After evidence of mating, females were weighed on gestational days 0, 7, 14 and 21 and on lactation days 1, 4, 7, 14 and 21.

Sperm parameters (parental animals):

Parameters examined in P male parental generations:
testis weight, epididymis weight, sperm count in epididymides, enumeration of cauda epididymal sperm reserve, sperm motility, sperm morphology.

Litter observations:

PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities.


GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; possible cause of death was determined for pups born or found dead.

Postmortem examinations (parental animals):

gross necroscopy on death, organ weights and microscopic examination on termination
SACRIFICE
- Male animals: All surviving animals after completion of female parturition.
- Maternal animals: All surviving animals that delivered on lactation day 21; females that failed to deliver were sacrificed on gestation day 25.

GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.

Postmortem examinations (offspring):

SACRIFICE
- These animals were subjected to macroscopic postmortem examinations


GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.

Statistics:

ANOVA for body weights, changes, food consumption, semen parameters, organ weights.

Reproductive indices:

yes

Offspring viability indices:

yes

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Other effects:

not specified

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

There were no remarkable findings in F0 males, with the exception of post dosing salivation.
in F0 females, there were no remarkable findings with the exception of negative ammonium sulfide staining in two high dose and one mid dose animal.

Dose descriptor:

NOAEL

Effect level:

> 500 mg/kg bw/day (actual dose received)

Sex:

male/female

Basis for effect level:

other: No significant adverse effects occurred at 500 mg/kg/bwt (highest dose tested).

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

There were no remarkable observations in F1 animals.

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

> 500 mg/kg bw/day (actual dose received)

Sex:

male/female

Basis for effect level:

other: No adverse effects occurred in animals in the top dose group, therefore a NOAEL cannot be identified from this study.

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Reproductive effects observed:

not specified

Conclusions:

Adverse effects did not occur in parental animals or offspring at doses up to 500 mg/kg bw/day, therefore NOAELs cannot be identified from this study.

Executive summary:

In a 1-generation reproduction study, benzenesulfonic acid, C14-C24 branched and linear alkyl derivatives was administered to 28 Sprague-Dawley rats/sex/via gavage at dose levels of 0, 50, 167 and 500 mg/kg bw/day.

 

No substance related effects occurred in treated animals. As no effects occurred at the highest dose, a NOAEL cannot be identified, and is greater than 500 mg/kg bw/day for reproductive and developmental toxicity.

  

This study is acceptable, and satisfies the guideline requirement for a 1-generation reproductive study; OECD 415 in rats. 

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

500 mg/kg bw/day

Species:

rat

Additional information

No adverse effect observed

Justification for selection of Effect on fertility via oral route:

Adverse effects did not occur in parental animals or offspring at doses up to 500 mg/kg bw/day, therefore NOAELs cannot be identified from this study.

Effects on developmental toxicity

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is of low toxicological activity (no evidence of toxicity seen in any of the tests available), it can be proven from toxicokinetic data that no systemic absorption occurs via relevant routes of exposure (e.g. plasma/blood concentrations below detection limit using a sensitive method and absence of the substance and of metabolites of the substance in urine, bile or exhaled air) and there is no or no significant human exposure

Species:

rat

Abnormalities:

not specified

Developmental effects observed:

not specified

Conclusions:

Based upon the toxicological data available, including the reproduction toxicity study available, and taking account of animal welfare consideration, there is no evidence that the substance is likely to have any developmental toxicity effect. It is therefore considered not scientifically justified to undertake a development toxicity study in animals.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available (further information necessary)

Additional information

Although just one study is available to assess the reproduction toxicity of the substance, the data available

suggests that the substance presents no potential of reproduction toxicity.

The following information is taken into account for any hazard / risk assessment:

One study is available to assess the reproduction toxicity of the substance by oral exposure.

Justification for selection of Effect on developmental toxicity: via oral route:

study technically not feasible

Toxicity to reproduction: other studies

Additional information

Based on the data available and considering the complete absence of response in that study, the substance is

considered to be not classified as a reproductive toxin.

Justification for classification or non-classification

No adverse effect observed