Registration Dossier

Administrative data

Endpoint:
one-generation reproductive toxicity
Remarks:
based on test guideline (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: study meets the criteria for Klimisch code 1.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]
Deviations:
no
GLP compliance:
yes
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
The test article (CAS 115733-09-0) is from the same chemical group (alkaryl sulfonates) as the submission substance

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: (P) males 5 wks, females 7 weeks; (F1) x wks
- Weight at study initiation: (P) Males: 154-197 g; Females: 139-184 g; (F1) Males: x-x g; Females: x-x g
- Housing: Suspended wire cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Corn oil was added to the test substance to acheive 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 (how): 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
Doses / concentrations
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.

Examinations

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 maroscopic 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

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

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 / performance (P0)

Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed

Details on results (P0)

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

Effect levels (P0)

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

Results: F1 generation

General toxicity (F1)

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

Details on results (F1)

There were no remakable observations in F1 animals.

Effect levels (F1)

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 occured 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

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

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.