Benzenesulfonic acid, para-, monoalkylation products with C14-C18 branched olefins (C15 rich) derived from propene oligomerization, calcium salt, overbased including distillates (petroleum), hydrotreated, solvent-refined, solvent-dewaxed, or catalytic dewaxed, light or heavy paraffinic C15-C50

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Remarks:

based on test guideline (migrated information)

Type of information:

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

Adequacy of study:

key study

Study period:

2003-2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was performed fully compliant to the OECD 415 Guideline and according to

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

Cas Number:

115733-09-0

Molecular formula:

Not available for UVCB substances

Constituent 2

Reference substance name:

Benzenesulfonic acid, C14-C24 branched & linear alkyl derivs. Calcium salts

IUPAC Name:

Benzenesulfonic acid, C14-C24 branched & linear alkyl derivs. Calcium salts

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: (P) approximately 7 wks (males), approximately 8 weeks (femlaes)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

Doses were selected following a range-finding study conducted according to OCED Test Guideline 407.

Details on mating procedure:

1 male mated to 1 female from the same group until evidence of mating (presence of copulatory plug or sperm) was observed. If evidence of mating was not observed, mating was discontinued after three weeks.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Homogeneity, stability and weekly dose concentration confirmation

Duration of treatment / exposure:

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

Frequency of treatment:

Once per day; 7 days per week

Details on study schedule:

- F0 Generation:
All F0 males were dosed for 70 days prior to mating and through the completion of parturition. All F0 females were dosed for 14 days prior to mating and through day 20 of lactation. All F0 animals were examined twice daily for appearance and behavior. Detailed clinical observations were performed weekly and cage side observations were performed daily approximately 30 to 120 minutes post dosing. Body weights were recorded weekly for both sexes prior to mating; maternal body weights were recorded on gestation days 0, 7, 14 and 21 as well as on lactation days 1, 4, 7, 14 and 21. Food consumption was recorded on the same days as body weights except during the mating period and during lactation. Animals were paired 1:1 for mating. Positive evidence of mating was confirmed by the presence of sperm or a vaginal copulatory plug (day 0 of gestation). If evidence of mating was not present after three weeks, mating was discontinued. All of the surviving F0 females were allowed to deliver and rear their pups to lactation day 21. The offspring were potentially exposed to the test substance in utero and through nursing during lactation days 121 until euthanization on post-natal day 21. The surviving F0 dams were necropsied on lactation day 21, following a minimum of 60 days of dosing. The surviving F0 males were necropsied at the conclusion of parturition following a minimum of 96 days of dosing. F0 females that failed to deliver were necropsied on post-mating day 25 (with evidence of mating) or 25 days following the termination of the mating period (with no evidence of mating).

- F1 Generation:
On lactation day 4 each litter was randomly culled to a maximum of eight pups, 4/sex/litter, when possible. Detailed pup examinations were performed on lactation days 0, 4, 7, 14 and 21. Pup sex was determined on lactation day 0 and verified on lactation days 4, 7, 14 and 21. Individual pup weights were determined on lactation days 1, 4, 7 14 and 21. Pups that were stillborn, cannibalized or found dead were subjected to a gross necropsy with emphasis on developmental morphology. Pups culled on day 4 were subjected to an abbreviated gross necropsy with emphasis on the reproductive system. All surviving pups were euthanized on lactation day 21 and examined macroscopically. All internal gross lesions were preserved for possible future microscopic examination.

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 50, 167 and 500 mg/kg day
Basis:
no data

No. of animals per sex per dose:

28 F0 rats/sex/dose or control level.

Control animals:

yes

Details on study design:

Control groups: 28 F0 rats/sex/group in the control, low, mid and high dose groups

Positive control:

not applicable.

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily approximately 30-120 minutes post dosing

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: weekly prior to mating; maternal body weights were recorded on gestation days 0, 7, 14 and 21 as well as on lactation days 1, 4, 7, 14 and 21.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Time schedule: on the same days as bodyweights except during the mating period and druing lactation

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

OTHER:
- All F0 animals were examined daily for appearance and behaviour

Oestrous cyclicity (parental animals):

All males were dosed for 70 days prior to mating and all females were dosed for 14 days prior to dating to allow for a full cycle of dosing before mating.

Sperm parameters (parental animals):

Sperm was collected from all surviving F0 males and evaluated for sperm count, concentration, motility and morphology assessment.

Litter observations:

Detailed pup examinations were performed on lactation days 0, 4, 7, 14 and 21. Pup sex was determined on lactation day 0 and verified on lactation days 4, 7, 14 and 21. Individual pup weights were determined on lactation days 1, 4, 7 14 and 21. Pups that were stillborn, cannibalized or found dead were subjected to a gross necropsy with emphasis on developmental morphology. Pups culled on day 4 were subjected to an abbreviated gross necropsy with emphasis on the reproductive system. All surviving pups were euthanized on lactation day 21 and examined macroscopically. All internal gross lesions were preserved for possible future microscopic examination.

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: All surviving animals were necropsied at the conclusion of parturition following a minimum of 96 days of dosing
- Maternal animals: All surviving animals were necropsied on lactation day 21, following a minimum of 60 days of dosing. F0 females that failed to deliver were necropsided on post-mating day 25 (with evidence of mating) or 25 days following the termination of the mating period (with no evidence of mating)

HISTOPATHOLOGY / ORGAN WEIGHTS
- Organ weights were determined and microscopic examinations were conducted for all surviving control and high dose F0 animals. Tissues examined microscopically included the liver, kidney, brain, right epididymides, cervix, coagulation gland, overies, pituitary, prostate, seminal vesicles, testes, uterus, vagina and gross lesions. F0 animals from all groups found dead or sacrificed early were subjected to a gross necroscopy and the microscopic evaluation of all tissues.

Postmortem examinations (offspring):

PARAMETERS EXAMINED
- Detailed pup examinations were performed on lactation days 0, 4, 7, 14 and 21. Pup sez was determined on lactation day 0 and verified on lactation days 4, 7, 14 and 21. Individual pup weights were determined on the lactation days 1, 4, 7, 14 and 21. Pups that were stillborn, cannibalized or found dead were subjected to a gross necroscopy with emphasis on developmental morphology. Pups culled on day 4 were subjected to an abbreviated gross necroscopy with emphasis on the repreoductive system. All surviving pups were euthanized on lactation day 21 and examined macroscopically.

Statistics:

Body weights, body weight changes, food consumption, semen parameters, organ weights, number of days to mating, getation length, pup viability data, total pups delivered, pup body weights and mean live litter size were analyzed by ANOVA followed, as needed, by Dunnett's test. Count data were analyzed by Chi-Square test followeed by Fisher's Exact Test for copulation and fertility indices, pup sex ratios, number of live and dead pups/group and pup survival. All analysis were two-tailed with a minimum significane level of 5%.

Reproductive indices:

- F0 generation:
mating and fertility indicies were calculated.

Offspring viability indices:

Not reported.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

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:

no effects observed

Other effects:

not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

Details on results (P0)

F0 males exhibited a dose related increase in post dosing salivation and dark material around the nose in the mid and high dose groups The remaining F0 male parameters were unremarkable including: mean body weight and food consumption, mating and fertility indicies, absolute and relative organ weights, sperm evaluation parameters and macro and microscopic pathology.

The clinical signs of the Fo females were generally unremarkable. There were no toxicologically meaningful differences between the control low, mid and high dose groups with respect to F0 female mean body weights, body weight change, food consumption, mating and fertility indicies, precoital intervals or gestation length. A macroscopic finding observed in two high dose and one mid female sacrificed on post mating day 25 was a finding of negative ammonium sulfide staining in animals that failed to deliver and were euthanized on gestation day 25.

No other remarkable findings were noted in the F0 females at necropsy and no meaningful microscopic lesions were observed in any of the treated F0 females.

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

500 mg/kg bw (total dose)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No statistically significant effects were seen in the parental animals during the study and no statistically significant abnormalities were observed during necropsy, therefore the highest treatment level was considered the NOAEL.

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)

No treatement-related findings were noted in the F1 pups during lactation. No treatment-related gross necroscopy findings were evident in any of the F1 pups examined (stillborn, dead during lactation, culled or examined at scheduled sacrifice on lactation day 21).

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

500 mg/kg bw (total dose)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

Results of the homogeneity analysis indicate that the test material was homogenous in the vehicle and stable for ten days when stored under ambient conditions. Concentration analysis confirmed that the test material was at the appropriate concentration in the dosing solutions.

Applicant's summary and conclusion

Conclusions:

Based on the results of this study, it has been concluded that the 500 mg/kg/day dose level was the NOAEL for parental F0 and F1 pup toxicity

Executive summary:

A one-generation study was performed in line with OCED Guideline 415 to determine the effects of benzenesulfonic acid, C14 -C24 branched & linear alkyl derivs. calcium salts on rats.

Male and female rats were dosed with the test material once a day, 7 days a week for 70 days premating (males) and 14 days premating (females). One male was then mated to one female from the same group until evidence of mating was observed. All F0 males were dosed until parturition and all F0 females were dosed through to day 20 of lactation. Detailed clinical and cage side observations were performed. Body weights and food consumption were weighed at appropriate intervals throughout the study. Offspring were potentially exposed to the test material in utero and via lactation. Surviving F0 dams were necropsied on lactation day 21 and surviving males were necropsied at the conclusion of parturition. Organ weights were determined and microscropic examinations conducted for all surviving control and high dose F0 animals. Sperm was collected from all surviving F0 males and appropriate parameters determined.

On lactaion day 4, each litter was randonly culled to a maximum of 8 pups/litter (4/sex/litter where possible). Detailed pup examinations and individual pup weights were determined throughout the lactation period. All surviving pups at lactation day 21 were examined macroscopically.

F0 males exhibited a dose-related increase in post-dosing salivation and dark material around the nose in the mid and high dose groups. No effects were observed in any of the other parameters measured. No treatment-related findings were noted in the F1 pups during lactation.

Based on the results of this study, it has been concluded that the 500 mg/kg/day dose level was the NOAEL for parental F0 and F1 pup toxicity